2RVF

Solution NMR structure of Monosiga brevicollis CRK/CRKL homolog (crka1) SH2 domain

Summary for 2RVF

• Entry DOI: 10.2210/pdb2rvf/pdb
• NMR Information: BMRB: 11597
• Descriptor: Predicted protein (1 entity in total)
• Functional Keywords: signal transduction, phosphotyrosine-binding domain, signaling protein
• Biological source: Monosiga brevicollis (Choanoflagellate)
• Total number of polymer chains: 1
• Total formula weight: 11482.66

Authors

Kasai, T.,Pawlak, J.,Imamoto, A.,Kigawa, T. (deposition date: 2015-09-24, release date: 2016-09-21, Last modification date: 2024-05-15)

Primary citation

Shigeno-Nakazawa, Y.,Kasai, T.,Ki, S.,Kostyanovskaya, E.,Pawlak, J.,Yamagishi, J.,Okimoto, N.,Taiji, M.,Okada, M.,Westbrook, J.,Satta, Y.,Kigawa, T.,Imamoto, A.
A pre-metazoan origin of the CRK gene family and co-opted signaling network
Sci Rep, 6:34349-34349, 2016

PubMed Abstract: CRK and CRKL adapter proteins play essential roles in development and cancer through their SRC homology 2 and 3 (SH2 and SH3) domains. To gain insight into the origin of their shared functions, we have investigated their evolutionary history. We propose a term, crk/crkl ancestral (crka), for orthologs in invertebrates before the divergence of CRK and CRKL in the vertebrate ancestor. We have isolated two orthologs expressed in the choanoflagellate Monosiga brevicollis, a unicellular relative to the metazoans. Consistent with its highly-conserved three-dimensional structure, the SH2 domain of M. brevicollis crka1 can bind to the mammalian CRK/CRKL SH2 binding consensus phospho-YxxP, and to the SRC substrate/focal adhesion protein BCAR1 (p130) in the presence of activated SRC. These results demonstrate an ancient origin of the CRK/CRKL SH2-target recognition specificity. Although BCAR1 orthologs exist only in metazoans as identified by an N-terminal SH3 domain, YxxP motifs, and a C-terminal FAT-like domain, some pre-metazoan transmembrane proteins include several YxxP repeats in their cytosolic region, suggesting that they are remotely related to the BCAR1 substrate domain. Since the tyrosine kinase SRC also has a pre-metazoan origin, co-option of BCAR1-related sequences may have rewired the crka-dependent network to mediate adhesion signals in the metazoan ancestor.

PubMed: 27686861
DOI: 10.1038/srep34349

Experimental method

SOLUTION NMR