Loading…
A Structure-Based Database of Antibody Variable Domain Diversity
The diversity of natural antibodies is limited by the genetic mechanisms that engender diversity and the functional requirements of antigen binding. Using an in vitro-evolved autonomous heavy chain variable domain (V HH-RIG), we have investigated the limits of structurally-tolerated diversity in the...
Saved in:
| Published in: | Journal of molecular biology 2005-05, Vol.348 (3), p.699-709 |
|---|---|
| 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-c549t-bec389c4144187632e03b17a2295d60fb40581350992530eb59350c88a7820c93 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c549t-bec389c4144187632e03b17a2295d60fb40581350992530eb59350c88a7820c93 |
| container_end_page | 709 |
| container_issue | 3 |
| container_start_page | 699 |
| container_title | Journal of molecular biology |
| container_volume | 348 |
| creator | Bond, Christopher J. Wiesmann, Christian Marsters, James C. Sidhu, Sachdev S. |
| description | The diversity of natural antibodies is limited by the genetic mechanisms that engender diversity and the functional requirements of antigen binding. Using an
in vitro-evolved autonomous heavy chain variable domain (V
HH-RIG), we have investigated the limits of structurally-tolerated diversity in the three complementarity-determining regions and a fourth loop within the third framework region. We determined the X-ray crystal structure of the V
HH-RIG domain at 1.9
Å resolution and used it to guide the design of phage-displayed libraries encompassing the four loops. The libraries were subjected to selections for structural stability, and a database of structurally-tolerated sequences was compiled from the sequences of approximately 1000 unique clones. The results reveal that all four loops accommodate significantly greater diversity than is observed in nature. Thus, it appears that most sequence biases in the natural immune repertoire arise from factors other than structural constraints and, consequently, it should be possible to enhance the functions of antibodies significantly through
in vitro evolution. |
| doi_str_mv | 10.1016/j.jmb.2005.02.063 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_67743211</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S002228360500241X</els_id><sourcerecordid>20716182</sourcerecordid><originalsourceid>FETCH-LOGICAL-c549t-bec389c4144187632e03b17a2295d60fb40581350992530eb59350c88a7820c93</originalsourceid><addsrcrecordid>eNqFkT1v2zAQhokiReOk_QFdAk3ZpN6RIkUhSxw7_QACdGiTlSCpM0DDslxSCuB_Hxo20C2e7g547h3eh7GvCBUCqm_rat27igPICngFSnxgMwTdlloJfcFmAJyXXAt1ya5SWkMGRa0_sUuUmiul5Izdz4s_Y5z8OEUqH2yirlja0bq8FcOqmG_H4IZuX7zYGKzbULEcehu2xTK8Ukxh3H9mH1d2k-jLaV6z5--Pfxc_y6ffP34t5k-ll3U7lo680K2vsa5RN0pwAuGwsZy3slOwcjVIjUJC23IpgJxs8-G1to3m4FtxzW6Pubs4_JsojaYPydNmY7c0TMmopqkFRzwLcmhQoeZnQWxyWwqbDOIR9HFIKdLK7GLobdwbBHMQYdYmizAHEQa4ySLyz80pfHI9df8_Ts1n4O4IUC7tNVA0yQfaeupCJD-abgjvxL8BRsCVPw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17534617</pqid></control><display><type>article</type><title>A Structure-Based Database of Antibody Variable Domain Diversity</title><source>Elsevier</source><creator>Bond, Christopher J. ; Wiesmann, Christian ; Marsters, James C. ; Sidhu, Sachdev S.</creator><creatorcontrib>Bond, Christopher J. ; Wiesmann, Christian ; Marsters, James C. ; Sidhu, Sachdev S.</creatorcontrib><description>The diversity of natural antibodies is limited by the genetic mechanisms that engender diversity and the functional requirements of antigen binding. Using an
in vitro-evolved autonomous heavy chain variable domain (V
HH-RIG), we have investigated the limits of structurally-tolerated diversity in the three complementarity-determining regions and a fourth loop within the third framework region. We determined the X-ray crystal structure of the V
HH-RIG domain at 1.9
Å resolution and used it to guide the design of phage-displayed libraries encompassing the four loops. The libraries were subjected to selections for structural stability, and a database of structurally-tolerated sequences was compiled from the sequences of approximately 1000 unique clones. The results reveal that all four loops accommodate significantly greater diversity than is observed in nature. Thus, it appears that most sequence biases in the natural immune repertoire arise from factors other than structural constraints and, consequently, it should be possible to enhance the functions of antibodies significantly through
in vitro evolution.</description><identifier>ISSN: 0022-2836</identifier><identifier>EISSN: 1089-8638</identifier><identifier>DOI: 10.1016/j.jmb.2005.02.063</identifier><identifier>PMID: 15826665</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Amino Acid Sequence ; Animals ; antibody ; Antibody Diversity ; combinatorial mutagenesis ; Complementarity Determining Regions - chemistry ; Complementarity Determining Regions - genetics ; Crystallography, X-Ray ; Humans ; Immunoglobulin Heavy Chains - chemistry ; Immunoglobulin Heavy Chains - genetics ; Models, Molecular ; Molecular Sequence Data ; Peptide Library ; phage display ; protein engineering ; Protein Structure, Tertiary ; variable domain</subject><ispartof>Journal of molecular biology, 2005-05, Vol.348 (3), p.699-709</ispartof><rights>2005 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c549t-bec389c4144187632e03b17a2295d60fb40581350992530eb59350c88a7820c93</citedby><cites>FETCH-LOGICAL-c549t-bec389c4144187632e03b17a2295d60fb40581350992530eb59350c88a7820c93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15826665$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bond, Christopher J.</creatorcontrib><creatorcontrib>Wiesmann, Christian</creatorcontrib><creatorcontrib>Marsters, James C.</creatorcontrib><creatorcontrib>Sidhu, Sachdev S.</creatorcontrib><title>A Structure-Based Database of Antibody Variable Domain Diversity</title><title>Journal of molecular biology</title><addtitle>J Mol Biol</addtitle><description>The diversity of natural antibodies is limited by the genetic mechanisms that engender diversity and the functional requirements of antigen binding. Using an
in vitro-evolved autonomous heavy chain variable domain (V
HH-RIG), we have investigated the limits of structurally-tolerated diversity in the three complementarity-determining regions and a fourth loop within the third framework region. We determined the X-ray crystal structure of the V
HH-RIG domain at 1.9
Å resolution and used it to guide the design of phage-displayed libraries encompassing the four loops. The libraries were subjected to selections for structural stability, and a database of structurally-tolerated sequences was compiled from the sequences of approximately 1000 unique clones. The results reveal that all four loops accommodate significantly greater diversity than is observed in nature. Thus, it appears that most sequence biases in the natural immune repertoire arise from factors other than structural constraints and, consequently, it should be possible to enhance the functions of antibodies significantly through
in vitro evolution.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>antibody</subject><subject>Antibody Diversity</subject><subject>combinatorial mutagenesis</subject><subject>Complementarity Determining Regions - chemistry</subject><subject>Complementarity Determining Regions - genetics</subject><subject>Crystallography, X-Ray</subject><subject>Humans</subject><subject>Immunoglobulin Heavy Chains - chemistry</subject><subject>Immunoglobulin Heavy Chains - genetics</subject><subject>Models, Molecular</subject><subject>Molecular Sequence Data</subject><subject>Peptide Library</subject><subject>phage display</subject><subject>protein engineering</subject><subject>Protein Structure, Tertiary</subject><subject>variable domain</subject><issn>0022-2836</issn><issn>1089-8638</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><recordid>eNqFkT1v2zAQhokiReOk_QFdAk3ZpN6RIkUhSxw7_QACdGiTlSCpM0DDslxSCuB_Hxo20C2e7g547h3eh7GvCBUCqm_rat27igPICngFSnxgMwTdlloJfcFmAJyXXAt1ya5SWkMGRa0_sUuUmiul5Izdz4s_Y5z8OEUqH2yirlja0bq8FcOqmG_H4IZuX7zYGKzbULEcehu2xTK8Ukxh3H9mH1d2k-jLaV6z5--Pfxc_y6ffP34t5k-ll3U7lo680K2vsa5RN0pwAuGwsZy3slOwcjVIjUJC23IpgJxs8-G1to3m4FtxzW6Pubs4_JsojaYPydNmY7c0TMmopqkFRzwLcmhQoeZnQWxyWwqbDOIR9HFIKdLK7GLobdwbBHMQYdYmizAHEQa4ySLyz80pfHI9df8_Ts1n4O4IUC7tNVA0yQfaeupCJD-abgjvxL8BRsCVPw</recordid><startdate>20050506</startdate><enddate>20050506</enddate><creator>Bond, Christopher J.</creator><creator>Wiesmann, Christian</creator><creator>Marsters, James C.</creator><creator>Sidhu, Sachdev S.</creator><general>Elsevier Ltd</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>7QO</scope><scope>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20050506</creationdate><title>A Structure-Based Database of Antibody Variable Domain Diversity</title><author>Bond, Christopher J. ; Wiesmann, Christian ; Marsters, James C. ; Sidhu, Sachdev S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c549t-bec389c4144187632e03b17a2295d60fb40581350992530eb59350c88a7820c93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>antibody</topic><topic>Antibody Diversity</topic><topic>combinatorial mutagenesis</topic><topic>Complementarity Determining Regions - chemistry</topic><topic>Complementarity Determining Regions - genetics</topic><topic>Crystallography, X-Ray</topic><topic>Humans</topic><topic>Immunoglobulin Heavy Chains - chemistry</topic><topic>Immunoglobulin Heavy Chains - genetics</topic><topic>Models, Molecular</topic><topic>Molecular Sequence Data</topic><topic>Peptide Library</topic><topic>phage display</topic><topic>protein engineering</topic><topic>Protein Structure, Tertiary</topic><topic>variable domain</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bond, Christopher J.</creatorcontrib><creatorcontrib>Wiesmann, Christian</creatorcontrib><creatorcontrib>Marsters, James C.</creatorcontrib><creatorcontrib>Sidhu, Sachdev S.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of molecular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bond, Christopher J.</au><au>Wiesmann, Christian</au><au>Marsters, James C.</au><au>Sidhu, Sachdev S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Structure-Based Database of Antibody Variable Domain Diversity</atitle><jtitle>Journal of molecular biology</jtitle><addtitle>J Mol Biol</addtitle><date>2005-05-06</date><risdate>2005</risdate><volume>348</volume><issue>3</issue><spage>699</spage><epage>709</epage><pages>699-709</pages><issn>0022-2836</issn><eissn>1089-8638</eissn><abstract>The diversity of natural antibodies is limited by the genetic mechanisms that engender diversity and the functional requirements of antigen binding. Using an
in vitro-evolved autonomous heavy chain variable domain (V
HH-RIG), we have investigated the limits of structurally-tolerated diversity in the three complementarity-determining regions and a fourth loop within the third framework region. We determined the X-ray crystal structure of the V
HH-RIG domain at 1.9
Å resolution and used it to guide the design of phage-displayed libraries encompassing the four loops. The libraries were subjected to selections for structural stability, and a database of structurally-tolerated sequences was compiled from the sequences of approximately 1000 unique clones. The results reveal that all four loops accommodate significantly greater diversity than is observed in nature. Thus, it appears that most sequence biases in the natural immune repertoire arise from factors other than structural constraints and, consequently, it should be possible to enhance the functions of antibodies significantly through
in vitro evolution.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>15826665</pmid><doi>10.1016/j.jmb.2005.02.063</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-2836 |
| ispartof | Journal of molecular biology, 2005-05, Vol.348 (3), p.699-709 |
| issn | 0022-2836 1089-8638 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_67743211 |
| source | Elsevier |
| subjects | Amino Acid Sequence Animals antibody Antibody Diversity combinatorial mutagenesis Complementarity Determining Regions - chemistry Complementarity Determining Regions - genetics Crystallography, X-Ray Humans Immunoglobulin Heavy Chains - chemistry Immunoglobulin Heavy Chains - genetics Models, Molecular Molecular Sequence Data Peptide Library phage display protein engineering Protein Structure, Tertiary variable domain |
| title | A Structure-Based Database of Antibody Variable Domain Diversity |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-04T12%3A32%3A02IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20Structure-Based%20Database%20of%20Antibody%20Variable%20Domain%20Diversity&rft.jtitle=Journal%20of%20molecular%20biology&rft.au=Bond,%20Christopher%20J.&rft.date=2005-05-06&rft.volume=348&rft.issue=3&rft.spage=699&rft.epage=709&rft.pages=699-709&rft.issn=0022-2836&rft.eissn=1089-8638&rft_id=info:doi/10.1016/j.jmb.2005.02.063&rft_dat=%3Cproquest_cross%3E20716182%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c549t-bec389c4144187632e03b17a2295d60fb40581350992530eb59350c88a7820c93%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=17534617&rft_id=info:pmid/15826665&rfr_iscdi=true |