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
2GGR 2006-08-01 Solution structure of the C-terminal SH3 domain of c-CrkII
1M3C 2003-08-05 Solution structure of a circular form of the N-terminal SH3 domain (E132C, E133G, R191G mutant) from oncogene protein c-Crk
2EYV 2006-11-10 SH2 domain of CT10-Regulated Kinase
2EYX 2006-11-10 C-Terminal SH3 domain of CT10-Regulated Kinase
2L3P 2010-12-08 Structure of the prolyl cis isomer of the Crk Protein
2EYW 2006-11-10 N-terminal SH3 domain of CT10-Regulated Kinase
1M30 2003-08-05 Solution structure of N-terminal SH3 domain from oncogene protein c-Crk
2MS4 2015-09-09 Cyclophilin a complexed with a fragment of crk-ii
2L3S 2010-12-08 Structure of the autoinhibited Crk
2L3Q 2010-12-08 Structure of the prolyl trans isomer of the Crk Protein
2EYZ 2006-11-10 CT10-Regulated Kinase isoform II
1JU5 2002-11-06 Ternary complex of an Crk SH2 domain, Crk-derived phophopeptide, and Abl SH3 domain by NMR spectroscopy
2DVJ 2007-05-08 phosphorylated Crk-II
1M3B 2003-08-05 Solution structure of a circular form of the N-terminal SH3 domain (A134C, E135G, R191G mutant) from oncogene protein c-Crk.
2EYY 2006-11-10 CT10-Regulated Kinase isoform I
1M3A 2003-08-05 Solution structure of a circular form of the truncated N-terminal SH3 domain from oncogene protein c-Crk.
5UL6 2017-08-09 1.45 The molecular mechanisms by which NS1 of the 1918 Spanish influenza A virus hijack host protein-protein interactions
1CKA 1995-05-08 1.5 STRUCTURAL BASIS FOR THE SPECIFIC INTERACTION OF LYSINE-CONTAINING PROLINE-RICH PEPTIDES WITH THE N-TERMINAL SH3 DOMAIN OF C-CRK
5JN0 2017-08-09 1.68 CRK-II SH2 domain
6ATV 2018-08-08 1.75 The molecular mechanisms by which NS1 of the 1918 Spanish influenza A virus hijack host protein-protein interactions
5L23 2016-09-07 1.77 Crystal structure of the complex between the N-terminal SH3 domain of CrkII and a proline-rich ligand
5IH2 2016-06-29 1.8 Structure, thermodynamics, and the role of conformational dynamics in the interactions between the N-terminal SH3 domain of CrkII and proline-rich motifs in cAbl
1CKB 1995-05-08 1.9 STRUCTURAL BASIS FOR THE SPECIFIC INTERACTION OF LYSINE-CONTAINING PROLINE-RICH PEPTIDES WITH THE N-TERMINAL SH3 DOMAIN OF C-CRK
1B07 1999-01-06 2.5 CRK SH3 DOMAIN COMPLEXED WITH PEPTOID INHIBITOR

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