Linked Life Data

12551896

Source:http://linkedlifedata.com/resource/pubmed/id/12551896

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2003-4-7
pubmed:abstractText
Grb7, Grb10, and Grb14 are members of a distinct family of adapter proteins that interact with various receptor tyrosine kinases upon receptor activation. Proteins in this family contain several modular signaling domains including a pleckstrin homology (PH) domain, a BPS (between PH and SH2) domain, and a C-terminal Src homology 2 (SH2) domain. Although SH2 domains are typically monomeric, we show that the Grb10 SH2 domain and also full-length Grb10 gamma are dimeric in solution under physiologic conditions. The crystal structure of the Grb10 SH2 domain at 1.65-A resolution reveals a non-covalent dimer whose interface comprises residues within and flanking the C-terminal alpha helix, which are conserved in the Grb7/Grb10/Grb14 family but not in other SH2 domains. Val-522 in the BG loop (BG3) and Asp-500 in the EF loop (EF1) are positioned to interfere with the binding of the P+3 residue of a phosphopeptide ligand. These structural features of the Grb10 SH2 domain will favor binding of dimeric, turn-containing phosphotyrosine sequences, such as the phosphorylated activation loops in the two beta subunits of the insulin and insulin-like growth factor-1 receptors. Moreover, the structure suggests the mechanism by which the Grb7 SH2 domain binds selectively to pTyr-1139 (pYVNQ) in Her2, which along with Grb7 is co-amplified in human breast cancers.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
11
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13257-64
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12551896-Adaptor Proteins, Signal Transducing, pubmed-meshheading:12551896-Amino Acid Sequence, pubmed-meshheading:12551896-Binding Sites, pubmed-meshheading:12551896-Crystallography, X-Ray, pubmed-meshheading:12551896-Dimerization, pubmed-meshheading:12551896-GRB10 Adaptor Protein, pubmed-meshheading:12551896-GRB7 Adaptor Protein, pubmed-meshheading:12551896-Humans, pubmed-meshheading:12551896-Ligands, pubmed-meshheading:12551896-Molecular Sequence Data, pubmed-meshheading:12551896-Peptide Fragments, pubmed-meshheading:12551896-Protein Conformation, pubmed-meshheading:12551896-Protein Structure, Secondary, pubmed-meshheading:12551896-Proteins, pubmed-meshheading:12551896-Receptor, Epidermal Growth Factor, pubmed-meshheading:12551896-Sequence Alignment, pubmed-meshheading:12551896-Sequence Homology, Amino Acid, pubmed-meshheading:12551896-Solutions, pubmed-meshheading:12551896-Substrate Specificity, pubmed-meshheading:12551896-src Homology Domains
pubmed:year
2003
pubmed:articleTitle
Structural basis for dimerization of the Grb10 Src homology 2 domain. Implications for ligand specificity.
pubmed:affiliation
Skirball Institute of Biomolecular Medicine and Department of Pharmacology, New York University School of Medicine, New York, New York 10016, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.