3t6a | pdb_00003t6a
Structure of the C-terminal domain of BCAR3
Structural highlights
Function[BCAR3_HUMAN] May act as an adapter protein and couple activated growth factor receptors to a signaling pathway that regulates the proliferation in breast cancer cells. When overexpressed, it confers anti-estrogen resistance in breast cancer cell lines. May also be regulated by cellular adhesion to extracellular matrix proteins.[1] Publication Abstract from PubMedMembers of the novel SH2-containing protein (NSP) and Crk-associated substrate (Cas) protein families form multidomain signaling platforms that mediate cell migration and invasion through a collection of distinct signaling motifs. Members of each family interact via their respective C-terminal domains, but the mechanism of this association has remained enigmatic. Here we present the crystal structures of the C-terminal domain from the NSP protein BCAR3 and the complex of NSP3 with p130Cas. BCAR3 adopts the Cdc25-homology fold of Ras GTPase exchange factors, but it has a 'closed' conformation incapable of enzymatic activity. The structure of the NSP3-p130Cas complex reveals that this closed conformation is instrumental for interaction of NSP proteins with a focal adhesion-targeting domain present in Cas proteins. This enzyme-to-adaptor conversion enables high-affinity, yet promiscuous, interactions between NSP and Cas proteins and represents an unprecedented mechanistic paradigm linking cellular signaling networks. NSP-Cas protein structures reveal a promiscuous interaction module in cell signaling.,Mace PD, Wallez Y, Dobaczewska MK, Lee JJ, Robinson H, Pasquale EB, Riedl SJ Nat Struct Mol Biol. 2011 Nov 13. doi: 10.1038/nsmb.2152. PMID:22081014[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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