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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
1995-10-25
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pubmed:abstractText |
SH3 domains mediate intracellular protein-protein interactions through the recognition of proline-rich sequence motifs on cellular proteins. Structural analysis of the Src SH3 domain (Src SH3) complexed with proline-rich peptide ligands revealed three binding sites involved in this interaction: two hydrophobic interactions (between aliphatic proline dipeptides in the SH3 ligand and highly conserved aromatic residues on the surface of the SH3 domain), and one salt bridge (between Asp-99 of Src and an Arg three residues upstream of the conserved Pro-X-X-Pro motif in the ligand). We examined the importance of the arginine binding site of SH3 domains by comparing the binding properties of wild-type Src SH3 and Abl SH3 with those of a Src SH3 mutant containing a mutated arginine binding site (D99N) and Abl SH3 mutant constructs engineered to contain an arginine binding site (T98D and T98D/F91Y). We found that the D99N mutation diminished binding to most Src SH3-binding proteins in whole cell extracts; however, there was only a moderate reduction in binding to a small subset of Src SH3-binding proteins (including the Src substrate p68). p68 was shown to contain two Arg-containing Asp-99-dependent binding sites and one Asp-99-independent binding site which lacks an Arg. Moreover, substitution of Asp for Thr-98 in Abl SH3 changed the binding specificity of this domain and conferred the ability to recognize Arg-containing ligands. These results indicate that Asp-99 is important for Src SH3 binding specificity and that Asp-99-dependent binding interactions play a dominant role in Src SH3 recognition of cellular binding proteins, and they suggest the existence of two Src SH3 binding mechanisms, one requiring Asp-99 and the other independent of this residue.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/7565714-1280858,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7565714-1374686,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7565714-1379745,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7565714-1423600,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7565714-14731533,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7565714-1729596,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7565714-3047011,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7565714-3078956,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7565714-7510218,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7565714-7512694,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7565714-7512695,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7565714-7516469,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7565714-7525585,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7565714-7526465,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7565714-7534229,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7565714-7664083,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7565714-7687536,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7565714-7688265,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7565714-7799925,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7565714-7834743,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7565714-7929027,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7565714-7929055,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7565714-7988556,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7565714-8325872,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7565714-8438166
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Arginine,
http://linkedlifedata.com/resource/pubmed/chemical/Aspartic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/DEAD-box RNA Helicases,
http://linkedlifedata.com/resource/pubmed/chemical/Ddx5 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Heterogeneous-Nuclear...,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Proline,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-abl,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins pp60(c-src),
http://linkedlifedata.com/resource/pubmed/chemical/RNA Helicases,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ribonucleoproteins
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0270-7306
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
15
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5627-34
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:7565714-3T3 Cells,
pubmed-meshheading:7565714-Amino Acid Sequence,
pubmed-meshheading:7565714-Animals,
pubmed-meshheading:7565714-Arginine,
pubmed-meshheading:7565714-Aspartic Acid,
pubmed-meshheading:7565714-DEAD-box RNA Helicases,
pubmed-meshheading:7565714-Heterogeneous-Nuclear Ribonucleoproteins,
pubmed-meshheading:7565714-Mice,
pubmed-meshheading:7565714-Mice, Inbred BALB C,
pubmed-meshheading:7565714-Molecular Sequence Data,
pubmed-meshheading:7565714-Mutation,
pubmed-meshheading:7565714-Nuclear Proteins,
pubmed-meshheading:7565714-Peptides,
pubmed-meshheading:7565714-Phosphorylation,
pubmed-meshheading:7565714-Proline,
pubmed-meshheading:7565714-Protein Binding,
pubmed-meshheading:7565714-Protein Kinases,
pubmed-meshheading:7565714-Proto-Oncogene Proteins c-abl,
pubmed-meshheading:7565714-Proto-Oncogene Proteins pp60(c-src),
pubmed-meshheading:7565714-RNA Helicases,
pubmed-meshheading:7565714-Recombinant Fusion Proteins,
pubmed-meshheading:7565714-Ribonucleoproteins,
pubmed-meshheading:7565714-Structure-Activity Relationship
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pubmed:year |
1995
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pubmed:articleTitle |
Structure-function analysis of SH3 domains: SH3 binding specificity altered by single amino acid substitutions.
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pubmed:affiliation |
ARIAD Pharmaceuticals, Cambridge, Massachusetts 02139, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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