PDBsum entry 3t6g

Signaling protein, cell adhesion

PDB id: 3t6g

Contents

Protein chains

299 a.a.

134 a.a.

273 a.a.

Ligands

ACT

Waters ×59

PDB id:

3t6g

Name:

Signaling protein, cell adhesion

Title:

Structure of the complex between nsp3 (shep1) and p130cas

Structure:

Sh2 domain-containing protein 3c. Chain: a, c. Fragment: unp residues 539-860. Synonym: novel sh2-containing protein 3. Engineered: yes. Mutation: yes. Breast cancer anti-estrogen resistance protein 1. Chain: b, d. Fragment: unp residues 645-870.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: sh2d3c, nsp3, unq272/pro309/pro34088. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: bcar1, cas, cass1, crkas. Expression_system_taxid: 562

Resolution:

2.50Å R-factor: 0.200 R-free: 0.266

Authors:

P.D.Mace,H.Robinson,S.J.Riedl

Key ref:

P.D.Mace et al. (2011). NSP-Cas protein structures reveal a promiscuous interaction module in cell signaling. Nat Struct Biol, 18, 1381-1387. PubMed id: 22081014

Date:

28-Jul-11 Release date: 23-Nov-11

Protein chain

Q8N5H7  (SH2D3_HUMAN) -  SH2 domain-containing protein 3C from Homo sapiens

Seq: 860 a.a.

Struc: 299 a.a.*

Protein chains

P56945  (BCAR1_HUMAN) -  Breast cancer anti-estrogen resistance protein 1 from Homo sapiens

Seq: 870 a.a.

Struc: 134 a.a.

Protein chain

Q8N5H7  (SH2D3_HUMAN) -  SH2 domain-containing protein 3C from Homo sapiens

Seq: 860 a.a.

Struc: 273 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B, C, D: E.C.?

Nat Struct Biol 18:1381-1387 (2011)

PubMed id: 22081014

NSP-Cas protein structures reveal a promiscuous interaction module in cell signaling.

P.D.Mace, Y.Wallez, M.K.Dobaczewska, J.J.Lee, H.Robinson, E.B.Pasquale, S.J.Riedl.

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.