2fei | pdb_00002fei
Solution structure of the second SH3 domain of Human CMS protein
Structural highlights
DiseaseCD2AP_HUMAN Defects in CD2AP are the cause of susceptibility to focal segmental glomerulosclerosis type 3 (FSGS3) [MIM:607832. A renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and edema. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation.[1] FunctionCD2AP_HUMAN Seems to act as an adapter protein between membrane proteins and the actin cytoskeleton. May play a role in receptor clustering and cytoskeletal polarity in the junction between T-cell and antigen-presenting cell. May anchor the podocyte slit diaphragm to the actin cytoskeleton in renal glomerolus. Also required for cytokinesis.[2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedCMS, cas ligand with multiple Src homology 3 (SH3) domains, belongs to a family of ubiquitously expressed adaptor proteins. Among the CMS binding proteins, c-Cbl has been mostly extensively studied. It was reported that the motif PKPFPR (residues 824-829) of c-Cbl can bind to the N-terminus SH3 domains of CMS. Here we report the solution structure of the second SH3 domain of CMS (CMS_SH3_B), furthermore, we have identified that a peptide from residues 701 to 714 of c-Cbl (Cbl-p), i.e. MTPSSRPLRPLDTS, can specially bind to CMS_SH3_B using NMR chemical shift perturbation, suggesting that the peptide is a new potential CMS binding site. Among the peptide, TPSSRPLR is the core binding motif and Arg709 plays a key role in the interaction. Cbl-p binding interface on CMS_SH3_B along a hydrophobic channel is composed of RT loop, n-Src loop and beta4 strand and divided into three pockets. This work indicates the solution structure of CMS_SH3_B bears the canonical beta-beta-beta-beta-alpha-beta fold and a new binding site in c-Cbl involved in its interaction with CMS, which probably contributes to the clustering of CMS. All the information provided here should be beneficial for the future functional study of CMS. Solution structure of the second SH3 domain of human CMS and a newly identified binding site at the C-terminus of c-Cbl.,Yao B, Zhang J, Dai H, Sun J, Jiao Y, Tang Y, Wu J, Shi Y Biochim Biophys Acta. 2007 Jan;1774(1):35-43. Epub 2006 Oct 27. PMID:17188587[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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