Solution structure and folding characteristics of the C-terminal SH3 domain of c-Crk-II.


Abstract

Crk-II is a signaling adaptor protein that is involved in many cellular processes including apoptosis, proliferation, and differentiation. It has a modular domain architecture consisting of an Src homology 2 domain (SH2) followed by two Src homology 3 (SH3) domains. The structures and ligand-binding properties of the SH2 and the middle SH3 domains are well-characterized. Several studies suggest that the C-terminal SH3 domain plays an important regulatory role in the protein; however, no structural information is available on this domain, and relatively little is known about its binding partners. In the current work, we have solved the solution NMR structure of the C-terminal SH3 domain. The domain adopts the standard SH3 fold comprising a five-stranded beta barrel. In agreement with alignment and modeling studies, the structure indicates that the canonical-binding surface of the SH3 domain is unusually polar and suggests that this domain may not bind typical PXXP ligands or that it may bind them with reduced affinity. Thermodynamic and kinetic studies show that the domain folds in a reversible two-state manner and that the stability of the fold is similar to that observed for other SH3 domains. These studies offer some insight into the likely structural and thermodynamic consequences of point mutations in the cSH3 domain that are known to deregulate Crk-II function. Our results set the stage for a better understanding the role of the cSH3 domain in the context of the full-length protein. Study holds ProTherm entries: 20116 Extra Details: signaling adaptor protein, regulatory role, canonical-binding, SH3 domains

Submission Details

ID: qQiCGdhy3

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:52 p.m.

Version: 1

Publication Details
Muralidharan V;Dutta K;Cho J;Vila-Perello M;Raleigh DP;Cowburn D;Muir TW,Biochemistry (2006) Solution structure and folding characteristics of the C-terminal SH3 domain of c-Crk-II. PMID:16846230
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant PDB Entries

Structure ID Release Date Resolution Structure Title
2L3Q 2010-09-21T00:00:00+0000 0 Structure of the prolyl trans isomer of the Crk Protein
2L3S 2010-09-21T00:00:00+0000 0 Structure of the autoinhibited Crk
2L3P 2010-09-21T00:00:00+0000 0 Structure of the prolyl cis isomer of the Crk Protein
2DVJ 2006-07-31T00:00:00+0000 0 phosphorylated Crk-II
2EYY 2005-11-10T00:00:00+0000 0 CT10-Regulated Kinase isoform I
2EYZ 2005-11-10T00:00:00+0000 0 CT10-Regulated Kinase isoform II
2EYV 2005-11-10T00:00:00+0000 0 SH2 domain of CT10-Regulated Kinase
2EYW 2005-11-10T00:00:00+0000 0 N-terminal SH3 domain of CT10-Regulated Kinase
2EYX 2005-11-10T00:00:00+0000 0 C-Terminal SH3 domain of CT10-Regulated Kinase
6ATV 2017-08-29T00:00:00+0000 1.75 The molecular mechanisms by which NS1 of the 1918 Spanish influenza A virus hijack host protein-protein interactions

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
92.0 Adapter molecule crk P87378 CRK_XENLA
97.3 Adapter molecule crk Q04929 CRK_CHICK
99.3 Adapter molecule crk Q63768 CRK_RAT
100.0 Adapter molecule crk Q64010 CRK_MOUSE
100.0 Adapter molecule crk P46108 CRK_HUMAN