5O2Q

p130Cas SH3 domain Vinculin peptide chimera

Summary for 5O2Q

• Entry DOI: 10.2210/pdb5o2q/pdb
• NMR Information: BMRB: 34143
• Descriptor: Breast cancer anti-estrogen resistance 1,Vinculin (1 entity in total)
• Functional Keywords: sh3 domain, structure from cyana 3.97, p130cas
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 1
• Total formula weight: 10623.10

Authors

Hexnerova, R.,Veverka, V. (deposition date: 2017-05-22, release date: 2017-09-20, Last modification date: 2024-06-19)

Primary citation

Gemperle, J.,Hexnerova, R.,Lepsik, M.,Tesina, P.,Dibus, M.,Novotny, M.,Brabek, J.,Veverka, V.,Rosel, D.
Structural characterization of CAS SH3 domain selectivity and regulation reveals new CAS interaction partners.
Sci Rep, 7:8057-8057, 2017

PubMed Abstract: CAS is a docking protein downstream of the proto-oncogene Src with a role in invasion and metastasis of cancer cells. The CAS SH3 domain is indispensable for CAS-mediated signaling, but structural aspects of CAS SH3 ligand binding and regulation are not well understood. Here, we identified the consensus CAS SH3 binding motif and structurally characterized the CAS SH3 domain in complex with ligand. We revealed the requirement for an uncommon centrally localized lysine residue at position +2 of CAS SH3 ligands and two rather dissimilar optional anchoring residues, leucine and arginine, at position +5. We further expanded the knowledge of CAS SH3 ligand binding regulation by manipulating tyrosine 12 phosphorylation and confirmed the negative role of this phosphorylation on CAS SH3 ligand binding. Finally, by exploiting the newly identified binding requirements of the CAS SH3 domain, we predicted and experimentally verified two novel CAS SH3 binding partners, DOK7 and GLIS2.

PubMed: 28808245
DOI: 10.1038/s41598-017-08303-4

Experimental method

SOLUTION NMR