Loading…
Biophysical insights from a single chain camelid antibody directed against the Disrupted-in-Schizophrenia 1 protein
Accumulating evidence suggests an important role for the Disrupted-in-Schizophrenia 1 (DISC1) protein in neurodevelopment and chronic mental illness. In particular, the C-terminal 300 amino acids of DISC1 have been found to mediate important protein-protein interactions and to harbor functionally im...
Saved in:
| Published in: | PloS one 2018-01, Vol.13 (1), p.e0191162-e0191162 |
|---|---|
| Main Authors: | , , , , , , , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c692t-faee45b9cb10318ee7f88990f102bf787d4836cc2eea71fb4bb3bc5cd734be3 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c692t-faee45b9cb10318ee7f88990f102bf787d4836cc2eea71fb4bb3bc5cd734be3 |
| container_end_page | e0191162 |
| container_issue | 1 |
| container_start_page | e0191162 |
| container_title | PloS one |
| container_volume | 13 |
| creator | Yerabham, Antony S K Müller-Schiffmann, Andreas Ziehm, Tamar Stadler, Andreas Köber, Sabrina Indurkhya, Xela Marreiros, Rita Trossbach, Svenja V Bradshaw, Nicholas J Prikulis, Ingrid Willbold, Dieter Weiergräber, Oliver H Korth, Carsten |
| description | Accumulating evidence suggests an important role for the Disrupted-in-Schizophrenia 1 (DISC1) protein in neurodevelopment and chronic mental illness. In particular, the C-terminal 300 amino acids of DISC1 have been found to mediate important protein-protein interactions and to harbor functionally important phosphorylation sites and disease-associated polymorphisms. However, long disordered regions and oligomer-forming subdomains have so far impeded structural analysis. VHH domains derived from camelid heavy chain only antibodies are minimal antigen binding modules with appreciable solubility and stability, which makes them well suited for the stabilizing proteins prior to structural investigation. Here, we report on the generation of a VHH domain derived from an immunized Lama glama, displaying high affinity for the human DISC1 C region (aa 691-836), and its characterization by surface plasmon resonance, size exclusion chromatography and immunological techniques. The VHH-DISC1 (C region) complex was also used for structural investigation by small angle X-ray scattering analysis. In combination with molecular modeling, these data support predictions regarding the three-dimensional fold of this DISC1 segment as well as its steric arrangement in complex with our VHH antibody. |
| doi_str_mv | 10.1371/journal.pone.0191162 |
| format | article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1986672851</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A522513246</galeid><doaj_id>oai_doaj_org_article_9a019ce9669146ad935d7d90240306aa</doaj_id><sourcerecordid>A522513246</sourcerecordid><originalsourceid>FETCH-LOGICAL-c692t-faee45b9cb10318ee7f88990f102bf787d4836cc2eea71fb4bb3bc5cd734be3</originalsourceid><addsrcrecordid>eNqNk12L1DAUhoso7rr6D0QLguhFx3y0aXMjrOvXwMKCI96GND1ts3SSmqTi-OvN7HSXqeyF5CLhnOe8Sd7kJMlzjFaYlvjdtZ2ckcNqtAZWCHOMGXmQnGJOScYIog-P1ifJE--vESpoxdjj5ITERF7h4jTxH7Qd-53XSg6pNl53ffBp6-w2lanXphsgVb3UJlVyC4NuUmmCrm2zSxvtQAWIkS7mfUhDD-lH7d00xmimTbZRvf4T5R0YLVOcjs4G0OZp8qiVg4dn83yWbD5_-n7xNbu8-rK-OL_MFOMkZK0EyIuaqxojiiuAsq0qzlGLEanbsiqbvKJMKQIgS9zWeV3TWhWqKWleAz1LXh5Ux8F6MbvlBebRgpJUBY7E-kA0Vl6L0emtdDthpRY3Aes6IV3QagDBZXRYAWeM45zJhtOiKRuOSI4oYlJGrffzblO9hUaBCU4OC9FlxuhedPaXKEqW5whFgTezgLM_J_BBbLVXMAzSgJ1uzs0ZYlXOI_rqH_T-281UJ-MFtGlt3FftRcV5QUgkSM4itbqHiqOBrVbxa7U6xhcFbxcFkQnwO3Ry8l6sN9_-n736sWRfH7E9yCH03g5T0Nb4JZgfQOWs9w7aO5MxEvvOuHVD7DtDzJ0Ry14cP9Bd0W0r0L_SIQor</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1986672851</pqid></control><display><type>article</type><title>Biophysical insights from a single chain camelid antibody directed against the Disrupted-in-Schizophrenia 1 protein</title><source>Open Access: PubMed Central</source><source>Publicly Available Content (ProQuest)</source><creator>Yerabham, Antony S K ; Müller-Schiffmann, Andreas ; Ziehm, Tamar ; Stadler, Andreas ; Köber, Sabrina ; Indurkhya, Xela ; Marreiros, Rita ; Trossbach, Svenja V ; Bradshaw, Nicholas J ; Prikulis, Ingrid ; Willbold, Dieter ; Weiergräber, Oliver H ; Korth, Carsten</creator><contributor>Legname, Giuseppe</contributor><creatorcontrib>Yerabham, Antony S K ; Müller-Schiffmann, Andreas ; Ziehm, Tamar ; Stadler, Andreas ; Köber, Sabrina ; Indurkhya, Xela ; Marreiros, Rita ; Trossbach, Svenja V ; Bradshaw, Nicholas J ; Prikulis, Ingrid ; Willbold, Dieter ; Weiergräber, Oliver H ; Korth, Carsten ; Legname, Giuseppe</creatorcontrib><description>Accumulating evidence suggests an important role for the Disrupted-in-Schizophrenia 1 (DISC1) protein in neurodevelopment and chronic mental illness. In particular, the C-terminal 300 amino acids of DISC1 have been found to mediate important protein-protein interactions and to harbor functionally important phosphorylation sites and disease-associated polymorphisms. However, long disordered regions and oligomer-forming subdomains have so far impeded structural analysis. VHH domains derived from camelid heavy chain only antibodies are minimal antigen binding modules with appreciable solubility and stability, which makes them well suited for the stabilizing proteins prior to structural investigation. Here, we report on the generation of a VHH domain derived from an immunized Lama glama, displaying high affinity for the human DISC1 C region (aa 691-836), and its characterization by surface plasmon resonance, size exclusion chromatography and immunological techniques. The VHH-DISC1 (C region) complex was also used for structural investigation by small angle X-ray scattering analysis. In combination with molecular modeling, these data support predictions regarding the three-dimensional fold of this DISC1 segment as well as its steric arrangement in complex with our VHH antibody.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0191162</identifier><identifier>PMID: 29324815</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Amino Acid Sequence ; Amino acids ; Animals ; Antibodies ; Antigen-Antibody Complex - chemistry ; Antigen-Antibody Complex - genetics ; Antigen-Antibody Reactions ; Antigens ; Biochemistry ; Biology and Life Sciences ; Biophysical Phenomena ; Camelids, New World - genetics ; Camelids, New World - immunology ; Chains ; Chromatography ; Crystallography ; Development and progression ; Disc1 protein ; Epitope Mapping ; Female ; Genetic aspects ; Humans ; Immunization ; Immunoglobulin Heavy Chains - chemistry ; Immunoglobulin Heavy Chains - genetics ; Immunoglobulins ; Immunology ; Medicine and Health Sciences ; Mental disorders ; Mice ; Models, Molecular ; Molecular biology ; Molecular modelling ; Nerve tissue proteins ; Nerve Tissue Proteins - chemistry ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - immunology ; Neuropathology ; Neurosciences ; Peptide Fragments - chemistry ; Peptide Fragments - genetics ; Peptide Fragments - immunology ; Phosphorylation ; Physical Sciences ; Physiological aspects ; Protein interaction ; Protein Interaction Domains and Motifs ; Protein-protein interactions ; Proteins ; Research and Analysis Methods ; Scattering, Small Angle ; Schizophrenia ; Single-Chain Antibodies - chemistry ; Single-Chain Antibodies - genetics ; Size exclusion chromatography ; Small angle X ray scattering ; Solubility ; Structural analysis ; Surface Plasmon Resonance ; Three dimensional models ; X ray scattering ; X-Ray Diffraction</subject><ispartof>PloS one, 2018-01, Vol.13 (1), p.e0191162-e0191162</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>2018 Yerabham et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2018 Yerabham et al 2018 Yerabham et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-faee45b9cb10318ee7f88990f102bf787d4836cc2eea71fb4bb3bc5cd734be3</citedby><cites>FETCH-LOGICAL-c692t-faee45b9cb10318ee7f88990f102bf787d4836cc2eea71fb4bb3bc5cd734be3</cites><orcidid>0000-0003-1503-1822</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1986672851/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1986672851?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25752,27923,27924,37011,37012,44589,53790,53792,74897</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29324815$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Legname, Giuseppe</contributor><creatorcontrib>Yerabham, Antony S K</creatorcontrib><creatorcontrib>Müller-Schiffmann, Andreas</creatorcontrib><creatorcontrib>Ziehm, Tamar</creatorcontrib><creatorcontrib>Stadler, Andreas</creatorcontrib><creatorcontrib>Köber, Sabrina</creatorcontrib><creatorcontrib>Indurkhya, Xela</creatorcontrib><creatorcontrib>Marreiros, Rita</creatorcontrib><creatorcontrib>Trossbach, Svenja V</creatorcontrib><creatorcontrib>Bradshaw, Nicholas J</creatorcontrib><creatorcontrib>Prikulis, Ingrid</creatorcontrib><creatorcontrib>Willbold, Dieter</creatorcontrib><creatorcontrib>Weiergräber, Oliver H</creatorcontrib><creatorcontrib>Korth, Carsten</creatorcontrib><title>Biophysical insights from a single chain camelid antibody directed against the Disrupted-in-Schizophrenia 1 protein</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Accumulating evidence suggests an important role for the Disrupted-in-Schizophrenia 1 (DISC1) protein in neurodevelopment and chronic mental illness. In particular, the C-terminal 300 amino acids of DISC1 have been found to mediate important protein-protein interactions and to harbor functionally important phosphorylation sites and disease-associated polymorphisms. However, long disordered regions and oligomer-forming subdomains have so far impeded structural analysis. VHH domains derived from camelid heavy chain only antibodies are minimal antigen binding modules with appreciable solubility and stability, which makes them well suited for the stabilizing proteins prior to structural investigation. Here, we report on the generation of a VHH domain derived from an immunized Lama glama, displaying high affinity for the human DISC1 C region (aa 691-836), and its characterization by surface plasmon resonance, size exclusion chromatography and immunological techniques. The VHH-DISC1 (C region) complex was also used for structural investigation by small angle X-ray scattering analysis. In combination with molecular modeling, these data support predictions regarding the three-dimensional fold of this DISC1 segment as well as its steric arrangement in complex with our VHH antibody.</description><subject>Amino Acid Sequence</subject><subject>Amino acids</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antigen-Antibody Complex - chemistry</subject><subject>Antigen-Antibody Complex - genetics</subject><subject>Antigen-Antibody Reactions</subject><subject>Antigens</subject><subject>Biochemistry</subject><subject>Biology and Life Sciences</subject><subject>Biophysical Phenomena</subject><subject>Camelids, New World - genetics</subject><subject>Camelids, New World - immunology</subject><subject>Chains</subject><subject>Chromatography</subject><subject>Crystallography</subject><subject>Development and progression</subject><subject>Disc1 protein</subject><subject>Epitope Mapping</subject><subject>Female</subject><subject>Genetic aspects</subject><subject>Humans</subject><subject>Immunization</subject><subject>Immunoglobulin Heavy Chains - chemistry</subject><subject>Immunoglobulin Heavy Chains - genetics</subject><subject>Immunoglobulins</subject><subject>Immunology</subject><subject>Medicine and Health Sciences</subject><subject>Mental disorders</subject><subject>Mice</subject><subject>Models, Molecular</subject><subject>Molecular biology</subject><subject>Molecular modelling</subject><subject>Nerve tissue proteins</subject><subject>Nerve Tissue Proteins - chemistry</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nerve Tissue Proteins - immunology</subject><subject>Neuropathology</subject><subject>Neurosciences</subject><subject>Peptide Fragments - chemistry</subject><subject>Peptide Fragments - genetics</subject><subject>Peptide Fragments - immunology</subject><subject>Phosphorylation</subject><subject>Physical Sciences</subject><subject>Physiological aspects</subject><subject>Protein interaction</subject><subject>Protein Interaction Domains and Motifs</subject><subject>Protein-protein interactions</subject><subject>Proteins</subject><subject>Research and Analysis Methods</subject><subject>Scattering, Small Angle</subject><subject>Schizophrenia</subject><subject>Single-Chain Antibodies - chemistry</subject><subject>Single-Chain Antibodies - genetics</subject><subject>Size exclusion chromatography</subject><subject>Small angle X ray scattering</subject><subject>Solubility</subject><subject>Structural analysis</subject><subject>Surface Plasmon Resonance</subject><subject>Three dimensional models</subject><subject>X ray scattering</subject><subject>X-Ray Diffraction</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L1DAUhoso7rr6D0QLguhFx3y0aXMjrOvXwMKCI96GND1ts3SSmqTi-OvN7HSXqeyF5CLhnOe8Sd7kJMlzjFaYlvjdtZ2ckcNqtAZWCHOMGXmQnGJOScYIog-P1ifJE--vESpoxdjj5ITERF7h4jTxH7Qd-53XSg6pNl53ffBp6-w2lanXphsgVb3UJlVyC4NuUmmCrm2zSxvtQAWIkS7mfUhDD-lH7d00xmimTbZRvf4T5R0YLVOcjs4G0OZp8qiVg4dn83yWbD5_-n7xNbu8-rK-OL_MFOMkZK0EyIuaqxojiiuAsq0qzlGLEanbsiqbvKJMKQIgS9zWeV3TWhWqKWleAz1LXh5Ux8F6MbvlBebRgpJUBY7E-kA0Vl6L0emtdDthpRY3Aes6IV3QagDBZXRYAWeM45zJhtOiKRuOSI4oYlJGrffzblO9hUaBCU4OC9FlxuhedPaXKEqW5whFgTezgLM_J_BBbLVXMAzSgJ1uzs0ZYlXOI_rqH_T-281UJ-MFtGlt3FftRcV5QUgkSM4itbqHiqOBrVbxa7U6xhcFbxcFkQnwO3Ry8l6sN9_-n736sWRfH7E9yCH03g5T0Nb4JZgfQOWs9w7aO5MxEvvOuHVD7DtDzJ0Ry14cP9Bd0W0r0L_SIQor</recordid><startdate>20180111</startdate><enddate>20180111</enddate><creator>Yerabham, Antony S K</creator><creator>Müller-Schiffmann, Andreas</creator><creator>Ziehm, Tamar</creator><creator>Stadler, Andreas</creator><creator>Köber, Sabrina</creator><creator>Indurkhya, Xela</creator><creator>Marreiros, Rita</creator><creator>Trossbach, Svenja V</creator><creator>Bradshaw, Nicholas J</creator><creator>Prikulis, Ingrid</creator><creator>Willbold, Dieter</creator><creator>Weiergräber, Oliver H</creator><creator>Korth, Carsten</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-1503-1822</orcidid></search><sort><creationdate>20180111</creationdate><title>Biophysical insights from a single chain camelid antibody directed against the Disrupted-in-Schizophrenia 1 protein</title><author>Yerabham, Antony S K ; Müller-Schiffmann, Andreas ; Ziehm, Tamar ; Stadler, Andreas ; Köber, Sabrina ; Indurkhya, Xela ; Marreiros, Rita ; Trossbach, Svenja V ; Bradshaw, Nicholas J ; Prikulis, Ingrid ; Willbold, Dieter ; Weiergräber, Oliver H ; Korth, Carsten</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-faee45b9cb10318ee7f88990f102bf787d4836cc2eea71fb4bb3bc5cd734be3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Amino Acid Sequence</topic><topic>Amino acids</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antigen-Antibody Complex - chemistry</topic><topic>Antigen-Antibody Complex - genetics</topic><topic>Antigen-Antibody Reactions</topic><topic>Antigens</topic><topic>Biochemistry</topic><topic>Biology and Life Sciences</topic><topic>Biophysical Phenomena</topic><topic>Camelids, New World - genetics</topic><topic>Camelids, New World - immunology</topic><topic>Chains</topic><topic>Chromatography</topic><topic>Crystallography</topic><topic>Development and progression</topic><topic>Disc1 protein</topic><topic>Epitope Mapping</topic><topic>Female</topic><topic>Genetic aspects</topic><topic>Humans</topic><topic>Immunization</topic><topic>Immunoglobulin Heavy Chains - chemistry</topic><topic>Immunoglobulin Heavy Chains - genetics</topic><topic>Immunoglobulins</topic><topic>Immunology</topic><topic>Medicine and Health Sciences</topic><topic>Mental disorders</topic><topic>Mice</topic><topic>Models, Molecular</topic><topic>Molecular biology</topic><topic>Molecular modelling</topic><topic>Nerve tissue proteins</topic><topic>Nerve Tissue Proteins - chemistry</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Nerve Tissue Proteins - immunology</topic><topic>Neuropathology</topic><topic>Neurosciences</topic><topic>Peptide Fragments - chemistry</topic><topic>Peptide Fragments - genetics</topic><topic>Peptide Fragments - immunology</topic><topic>Phosphorylation</topic><topic>Physical Sciences</topic><topic>Physiological aspects</topic><topic>Protein interaction</topic><topic>Protein Interaction Domains and Motifs</topic><topic>Protein-protein interactions</topic><topic>Proteins</topic><topic>Research and Analysis Methods</topic><topic>Scattering, Small Angle</topic><topic>Schizophrenia</topic><topic>Single-Chain Antibodies - chemistry</topic><topic>Single-Chain Antibodies - genetics</topic><topic>Size exclusion chromatography</topic><topic>Small angle X ray scattering</topic><topic>Solubility</topic><topic>Structural analysis</topic><topic>Surface Plasmon Resonance</topic><topic>Three dimensional models</topic><topic>X ray scattering</topic><topic>X-Ray Diffraction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yerabham, Antony S K</creatorcontrib><creatorcontrib>Müller-Schiffmann, Andreas</creatorcontrib><creatorcontrib>Ziehm, Tamar</creatorcontrib><creatorcontrib>Stadler, Andreas</creatorcontrib><creatorcontrib>Köber, Sabrina</creatorcontrib><creatorcontrib>Indurkhya, Xela</creatorcontrib><creatorcontrib>Marreiros, Rita</creatorcontrib><creatorcontrib>Trossbach, Svenja V</creatorcontrib><creatorcontrib>Bradshaw, Nicholas J</creatorcontrib><creatorcontrib>Prikulis, Ingrid</creatorcontrib><creatorcontrib>Willbold, Dieter</creatorcontrib><creatorcontrib>Weiergräber, Oliver H</creatorcontrib><creatorcontrib>Korth, Carsten</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Science (Gale in Context)</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>ProQuest Nursing and Allied Health Journals</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>ProQuest - Health & Medical Complete保健、医学与药学数据库</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>Biological Sciences</collection><collection>Agriculture Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content (ProQuest)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yerabham, Antony S K</au><au>Müller-Schiffmann, Andreas</au><au>Ziehm, Tamar</au><au>Stadler, Andreas</au><au>Köber, Sabrina</au><au>Indurkhya, Xela</au><au>Marreiros, Rita</au><au>Trossbach, Svenja V</au><au>Bradshaw, Nicholas J</au><au>Prikulis, Ingrid</au><au>Willbold, Dieter</au><au>Weiergräber, Oliver H</au><au>Korth, Carsten</au><au>Legname, Giuseppe</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Biophysical insights from a single chain camelid antibody directed against the Disrupted-in-Schizophrenia 1 protein</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2018-01-11</date><risdate>2018</risdate><volume>13</volume><issue>1</issue><spage>e0191162</spage><epage>e0191162</epage><pages>e0191162-e0191162</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Accumulating evidence suggests an important role for the Disrupted-in-Schizophrenia 1 (DISC1) protein in neurodevelopment and chronic mental illness. In particular, the C-terminal 300 amino acids of DISC1 have been found to mediate important protein-protein interactions and to harbor functionally important phosphorylation sites and disease-associated polymorphisms. However, long disordered regions and oligomer-forming subdomains have so far impeded structural analysis. VHH domains derived from camelid heavy chain only antibodies are minimal antigen binding modules with appreciable solubility and stability, which makes them well suited for the stabilizing proteins prior to structural investigation. Here, we report on the generation of a VHH domain derived from an immunized Lama glama, displaying high affinity for the human DISC1 C region (aa 691-836), and its characterization by surface plasmon resonance, size exclusion chromatography and immunological techniques. The VHH-DISC1 (C region) complex was also used for structural investigation by small angle X-ray scattering analysis. In combination with molecular modeling, these data support predictions regarding the three-dimensional fold of this DISC1 segment as well as its steric arrangement in complex with our VHH antibody.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29324815</pmid><doi>10.1371/journal.pone.0191162</doi><tpages>e0191162</tpages><orcidid>https://orcid.org/0000-0003-1503-1822</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2018-01, Vol.13 (1), p.e0191162-e0191162 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1986672851 |
| source | Open Access: PubMed Central; Publicly Available Content (ProQuest) |
| subjects | Amino Acid Sequence Amino acids Animals Antibodies Antigen-Antibody Complex - chemistry Antigen-Antibody Complex - genetics Antigen-Antibody Reactions Antigens Biochemistry Biology and Life Sciences Biophysical Phenomena Camelids, New World - genetics Camelids, New World - immunology Chains Chromatography Crystallography Development and progression Disc1 protein Epitope Mapping Female Genetic aspects Humans Immunization Immunoglobulin Heavy Chains - chemistry Immunoglobulin Heavy Chains - genetics Immunoglobulins Immunology Medicine and Health Sciences Mental disorders Mice Models, Molecular Molecular biology Molecular modelling Nerve tissue proteins Nerve Tissue Proteins - chemistry Nerve Tissue Proteins - genetics Nerve Tissue Proteins - immunology Neuropathology Neurosciences Peptide Fragments - chemistry Peptide Fragments - genetics Peptide Fragments - immunology Phosphorylation Physical Sciences Physiological aspects Protein interaction Protein Interaction Domains and Motifs Protein-protein interactions Proteins Research and Analysis Methods Scattering, Small Angle Schizophrenia Single-Chain Antibodies - chemistry Single-Chain Antibodies - genetics Size exclusion chromatography Small angle X ray scattering Solubility Structural analysis Surface Plasmon Resonance Three dimensional models X ray scattering X-Ray Diffraction |
| title | Biophysical insights from a single chain camelid antibody directed against the Disrupted-in-Schizophrenia 1 protein |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-13T03%3A20%3A58IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Biophysical%20insights%20from%20a%20single%20chain%20camelid%20antibody%20directed%20against%20the%20Disrupted-in-Schizophrenia%201%20protein&rft.jtitle=PloS%20one&rft.au=Yerabham,%20Antony%20S%20K&rft.date=2018-01-11&rft.volume=13&rft.issue=1&rft.spage=e0191162&rft.epage=e0191162&rft.pages=e0191162-e0191162&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0191162&rft_dat=%3Cgale_plos_%3EA522513246%3C/gale_plos_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c692t-faee45b9cb10318ee7f88990f102bf787d4836cc2eea71fb4bb3bc5cd734be3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1986672851&rft_id=info:pmid/29324815&rft_galeid=A522513246&rfr_iscdi=true |