3T6A

Structure of the C-terminal domain of BCAR3

Summary for 3T6A

• Entry DOI: 10.2210/pdb3t6a/pdb
• Related: 3T6G
• Descriptor: Breast cancer anti-estrogen resistance protein 3, (20S)-2,5,8,11,14,17-HEXAMETHYL-3,6,9,12,15,18-HEXAOXAHENICOSANE-1,20-DIOL, UNKNOWN ATOM OR ION, ... (4 entities in total)
• Functional Keywords: cdc25-homology domain, gtpase exchange factor, signaling protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 152888.43

Authors

Mace, P.D.,Robinson, H.,Riedl, S.J. (deposition date: 2011-07-28, release date: 2011-11-23, Last modification date: 2024-02-28)

Primary citation

Mace, P.D.,Wallez, Y.,Dobaczewska, M.K.,Lee, J.J.,Robinson, H.,Pasquale, E.B.,Riedl, S.J.
NSP-Cas protein structures reveal a promiscuous interaction module in cell signaling.
Nat.Struct.Mol.Biol., 18:1381-1387, 2011

PubMed Abstract: Members 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.

PubMed: 22081014
DOI: 10.1038/nsmb.2152

Experimental method

X-RAY DIFFRACTION (2.4 Å)