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Solution structure of the receptor tyrosine kinase EphB2 SAM domain and identification of two distinct homotypic interaction sites
The sterile alpha motif (SAM) is a protein interaction domain of around 70 amino acids present predominantly in the N- and C-termini of more than 60 diverse proteins that participate in signal transduction and transcriptional repression. SAM domains have been shown to homo- and hetero-oligomerize an...
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Published in: | Protein science 1999-10, Vol.8 (10), p.1954-1961 |
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container_end_page | 1961 |
container_issue | 10 |
container_start_page | 1954 |
container_title | Protein science |
container_volume | 8 |
creator | SMALLA, MAIKA SCHMIEDER, PETER KELLY, MARK TER LAAK, ANTONIUS KRAUSE, GERD BALL, LINDA WAHL, MARTIN BORK, PEER OSCHKINAT, HARTMUT |
description | The sterile alpha motif (SAM) is a protein interaction domain
of around 70 amino acids present predominantly in the N-
and C-termini of more than 60 diverse proteins that participate
in signal transduction and transcriptional repression.
SAM domains have been shown to homo- and hetero-oligomerize
and to mediate specific protein–protein interactions.
A highly conserved subclass of SAM domains is present at
the intracellular C-terminus of more than 40 Eph receptor
tyrosine kinases that are involved in the control of axonal
pathfinding upon ephrin-induced oligomerization and activation
in the event of cell–cell contacts. These SAM domains
appear to participate in downstream signaling events via
interactions with cytosolic proteins. We determined the solution structure of the EphB2 receptor
SAM domain and studied its association behavior. The structure
consists of five helices forming a compact structure without
binding pockets or exposed conserved aromatic residues.
Concentration-dependent chemical shift changes of NMR signals
reveal two distinct well-separated areas on the domains'
surface sensitive to the formation of homotypic oligomers
in solution. These findings are supported by analytical
ultracentrifugation studies. The conserved Tyr932, which
was reported to be essential for the interaction with SH2
domains after phosphorylation, is buried in the hydrophobic
core of the structure. The weak capability of the isolated EphB2 receptor SAM domain
to form oligomers is supposed to be relevant in vivo when
the driving force of ligand binding induces receptor oligomerization.
A formation of SAM tetramers is thought to provide an appropriate
contact area for the binding of a low-molecular-weight
phosphotyrosine phosphatase and to initiate further downstream
responses. |
doi_str_mv | 10.1110/ps.8.10.1954 |
format | article |
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of around 70 amino acids present predominantly in the N-
and C-termini of more than 60 diverse proteins that participate
in signal transduction and transcriptional repression.
SAM domains have been shown to homo- and hetero-oligomerize
and to mediate specific protein–protein interactions.
A highly conserved subclass of SAM domains is present at
the intracellular C-terminus of more than 40 Eph receptor
tyrosine kinases that are involved in the control of axonal
pathfinding upon ephrin-induced oligomerization and activation
in the event of cell–cell contacts. These SAM domains
appear to participate in downstream signaling events via
interactions with cytosolic proteins. We determined the solution structure of the EphB2 receptor
SAM domain and studied its association behavior. The structure
consists of five helices forming a compact structure without
binding pockets or exposed conserved aromatic residues.
Concentration-dependent chemical shift changes of NMR signals
reveal two distinct well-separated areas on the domains'
surface sensitive to the formation of homotypic oligomers
in solution. These findings are supported by analytical
ultracentrifugation studies. The conserved Tyr932, which
was reported to be essential for the interaction with SH2
domains after phosphorylation, is buried in the hydrophobic
core of the structure. The weak capability of the isolated EphB2 receptor SAM domain
to form oligomers is supposed to be relevant in vivo when
the driving force of ligand binding induces receptor oligomerization.
A formation of SAM tetramers is thought to provide an appropriate
contact area for the binding of a low-molecular-weight
phosphotyrosine phosphatase and to initiate further downstream
responses.</description><identifier>ISSN: 0961-8368</identifier><identifier>EISSN: 1469-896X</identifier><identifier>DOI: 10.1110/ps.8.10.1954</identifier><identifier>PMID: 10548040</identifier><language>eng</language><publisher>Bristol: Cambridge University Press</publisher><subject>Amino Acid Motifs ; Amino Acid Sequence ; Biopolymers ; Eph receptor ; Magnetic Resonance Spectroscopy ; Models, Molecular ; Molecular Sequence Data ; oligomerization ; Phosphorylation ; Protein Conformation ; Receptor Protein-Tyrosine Kinases - chemistry ; Receptor Protein-Tyrosine Kinases - metabolism ; Receptor, EphB2 ; SAM domain ; Sequence Homology, Amino Acid ; Solutions ; Tyrosine - metabolism ; tyrosine phosphorylation</subject><ispartof>Protein science, 1999-10, Vol.8 (10), p.1954-1961</ispartof><rights>1999 The Protein Society</rights><rights>Copyright © 1999 The Protein Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4644-a36b03d679f4766efc91cbe7bdbbbc01ba8e3f52735dd84cba0875510377f1c73</citedby><cites>FETCH-LOGICAL-c4644-a36b03d679f4766efc91cbe7bdbbbc01ba8e3f52735dd84cba0875510377f1c73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2144140/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2144140/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10548040$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SMALLA, MAIKA</creatorcontrib><creatorcontrib>SCHMIEDER, PETER</creatorcontrib><creatorcontrib>KELLY, MARK</creatorcontrib><creatorcontrib>TER LAAK, ANTONIUS</creatorcontrib><creatorcontrib>KRAUSE, GERD</creatorcontrib><creatorcontrib>BALL, LINDA</creatorcontrib><creatorcontrib>WAHL, MARTIN</creatorcontrib><creatorcontrib>BORK, PEER</creatorcontrib><creatorcontrib>OSCHKINAT, HARTMUT</creatorcontrib><title>Solution structure of the receptor tyrosine kinase EphB2 SAM domain and identification of two distinct homotypic interaction sites</title><title>Protein science</title><addtitle>Protein Sci</addtitle><description>The sterile alpha motif (SAM) is a protein interaction domain
of around 70 amino acids present predominantly in the N-
and C-termini of more than 60 diverse proteins that participate
in signal transduction and transcriptional repression.
SAM domains have been shown to homo- and hetero-oligomerize
and to mediate specific protein–protein interactions.
A highly conserved subclass of SAM domains is present at
the intracellular C-terminus of more than 40 Eph receptor
tyrosine kinases that are involved in the control of axonal
pathfinding upon ephrin-induced oligomerization and activation
in the event of cell–cell contacts. These SAM domains
appear to participate in downstream signaling events via
interactions with cytosolic proteins. We determined the solution structure of the EphB2 receptor
SAM domain and studied its association behavior. The structure
consists of five helices forming a compact structure without
binding pockets or exposed conserved aromatic residues.
Concentration-dependent chemical shift changes of NMR signals
reveal two distinct well-separated areas on the domains'
surface sensitive to the formation of homotypic oligomers
in solution. These findings are supported by analytical
ultracentrifugation studies. The conserved Tyr932, which
was reported to be essential for the interaction with SH2
domains after phosphorylation, is buried in the hydrophobic
core of the structure. The weak capability of the isolated EphB2 receptor SAM domain
to form oligomers is supposed to be relevant in vivo when
the driving force of ligand binding induces receptor oligomerization.
A formation of SAM tetramers is thought to provide an appropriate
contact area for the binding of a low-molecular-weight
phosphotyrosine phosphatase and to initiate further downstream
responses.</description><subject>Amino Acid Motifs</subject><subject>Amino Acid Sequence</subject><subject>Biopolymers</subject><subject>Eph receptor</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Models, Molecular</subject><subject>Molecular Sequence Data</subject><subject>oligomerization</subject><subject>Phosphorylation</subject><subject>Protein Conformation</subject><subject>Receptor Protein-Tyrosine Kinases - chemistry</subject><subject>Receptor Protein-Tyrosine Kinases - metabolism</subject><subject>Receptor, EphB2</subject><subject>SAM domain</subject><subject>Sequence Homology, Amino Acid</subject><subject>Solutions</subject><subject>Tyrosine - metabolism</subject><subject>tyrosine phosphorylation</subject><issn>0961-8368</issn><issn>1469-896X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><recordid>eNp9kU1rFTEUhoMo9lrduZasXDnXZCaTyWyEWqottFSsgruQjzO9qTPJNMlY7tZf7tzORVoQV-GQh-e8nBeh15SsKaXk_ZjWYr0b2po9QSvKeFuIlv94ilak5bQQFRcH6EVKN4QQRsvqOTqgpGaCMLJCv69CP2UXPE45TiZPEXDocN4AjmBgzCHivI0hOQ_4p_MqAT4ZNx9LfHV0gW0YlPNYeYudBZ9d54y6t-0cdwFbl7LzJuNNGELejs5g5zNEZZadLkN6iZ51qk_wav8eou-fTr4dnxbnl5_Pjo_OC8M4Y4WquCaV5U3bsYZz6ExLjYZGW621IVQrAVVXl01VWyuY0YqIpq4pqZqmo6apDtGHxTtOegBr5rxR9XKMblBxK4Ny8vGPdxt5HX7JkjJGGZkFb_eCGG4nSFkOLhnoe-UhTEnytixrUdUz-G4BzXy4FKH7u4QSuStNjkmK-2EubcbfPAz2AF5amgG2AHeuh-1_ZfLL10tByd673sdQg47OXoO8CVP085H_HeQPm2C2OQ</recordid><startdate>19991001</startdate><enddate>19991001</enddate><creator>SMALLA, MAIKA</creator><creator>SCHMIEDER, PETER</creator><creator>KELLY, MARK</creator><creator>TER LAAK, ANTONIUS</creator><creator>KRAUSE, GERD</creator><creator>BALL, LINDA</creator><creator>WAHL, MARTIN</creator><creator>BORK, PEER</creator><creator>OSCHKINAT, HARTMUT</creator><general>Cambridge University Press</general><general>Cold Spring Harbor Laboratory Press</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>19991001</creationdate><title>Solution structure of the receptor tyrosine kinase EphB2 SAM domain and identification of two distinct homotypic interaction sites</title><author>SMALLA, MAIKA ; SCHMIEDER, PETER ; KELLY, MARK ; TER LAAK, ANTONIUS ; KRAUSE, GERD ; BALL, LINDA ; WAHL, MARTIN ; BORK, PEER ; OSCHKINAT, HARTMUT</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4644-a36b03d679f4766efc91cbe7bdbbbc01ba8e3f52735dd84cba0875510377f1c73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Amino Acid Motifs</topic><topic>Amino Acid Sequence</topic><topic>Biopolymers</topic><topic>Eph receptor</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Models, Molecular</topic><topic>Molecular Sequence Data</topic><topic>oligomerization</topic><topic>Phosphorylation</topic><topic>Protein Conformation</topic><topic>Receptor Protein-Tyrosine Kinases - chemistry</topic><topic>Receptor Protein-Tyrosine Kinases - metabolism</topic><topic>Receptor, EphB2</topic><topic>SAM domain</topic><topic>Sequence Homology, Amino Acid</topic><topic>Solutions</topic><topic>Tyrosine - metabolism</topic><topic>tyrosine phosphorylation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SMALLA, MAIKA</creatorcontrib><creatorcontrib>SCHMIEDER, PETER</creatorcontrib><creatorcontrib>KELLY, MARK</creatorcontrib><creatorcontrib>TER LAAK, ANTONIUS</creatorcontrib><creatorcontrib>KRAUSE, GERD</creatorcontrib><creatorcontrib>BALL, LINDA</creatorcontrib><creatorcontrib>WAHL, MARTIN</creatorcontrib><creatorcontrib>BORK, PEER</creatorcontrib><creatorcontrib>OSCHKINAT, HARTMUT</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Protein science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SMALLA, MAIKA</au><au>SCHMIEDER, PETER</au><au>KELLY, MARK</au><au>TER LAAK, ANTONIUS</au><au>KRAUSE, GERD</au><au>BALL, LINDA</au><au>WAHL, MARTIN</au><au>BORK, PEER</au><au>OSCHKINAT, HARTMUT</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Solution structure of the receptor tyrosine kinase EphB2 SAM domain and identification of two distinct homotypic interaction sites</atitle><jtitle>Protein science</jtitle><addtitle>Protein Sci</addtitle><date>1999-10-01</date><risdate>1999</risdate><volume>8</volume><issue>10</issue><spage>1954</spage><epage>1961</epage><pages>1954-1961</pages><issn>0961-8368</issn><eissn>1469-896X</eissn><abstract>The sterile alpha motif (SAM) is a protein interaction domain
of around 70 amino acids present predominantly in the N-
and C-termini of more than 60 diverse proteins that participate
in signal transduction and transcriptional repression.
SAM domains have been shown to homo- and hetero-oligomerize
and to mediate specific protein–protein interactions.
A highly conserved subclass of SAM domains is present at
the intracellular C-terminus of more than 40 Eph receptor
tyrosine kinases that are involved in the control of axonal
pathfinding upon ephrin-induced oligomerization and activation
in the event of cell–cell contacts. These SAM domains
appear to participate in downstream signaling events via
interactions with cytosolic proteins. We determined the solution structure of the EphB2 receptor
SAM domain and studied its association behavior. The structure
consists of five helices forming a compact structure without
binding pockets or exposed conserved aromatic residues.
Concentration-dependent chemical shift changes of NMR signals
reveal two distinct well-separated areas on the domains'
surface sensitive to the formation of homotypic oligomers
in solution. These findings are supported by analytical
ultracentrifugation studies. The conserved Tyr932, which
was reported to be essential for the interaction with SH2
domains after phosphorylation, is buried in the hydrophobic
core of the structure. The weak capability of the isolated EphB2 receptor SAM domain
to form oligomers is supposed to be relevant in vivo when
the driving force of ligand binding induces receptor oligomerization.
A formation of SAM tetramers is thought to provide an appropriate
contact area for the binding of a low-molecular-weight
phosphotyrosine phosphatase and to initiate further downstream
responses.</abstract><cop>Bristol</cop><pub>Cambridge University Press</pub><pmid>10548040</pmid><doi>10.1110/ps.8.10.1954</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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source | PubMed (Medline); Wiley-Blackwell Read & Publish Collection |
subjects | Amino Acid Motifs Amino Acid Sequence Biopolymers Eph receptor Magnetic Resonance Spectroscopy Models, Molecular Molecular Sequence Data oligomerization Phosphorylation Protein Conformation Receptor Protein-Tyrosine Kinases - chemistry Receptor Protein-Tyrosine Kinases - metabolism Receptor, EphB2 SAM domain Sequence Homology, Amino Acid Solutions Tyrosine - metabolism tyrosine phosphorylation |
title | Solution structure of the receptor tyrosine kinase EphB2 SAM domain and identification of two distinct homotypic interaction sites |
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