1ygu
From Proteopedia
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Crystal structure of the tandem phosphatase domains of RPTP CD45 with a pTyr peptide
Contents |
Overview
CD45 is the prototypic member of transmembrane receptor-like protein tyrosine phosphatases (RPTPs) and has essential roles in immune functions. The cytoplasmic region of CD45, like many other RPTPs, contains two homologous protein tyrosine phosphatase domains, active domain 1 (D1) and catalytically impaired domain 2 (D2). Here, we report crystal structure of the cytoplasmic D1D2 segment of human CD45 in native and phosphotyrosyl peptide-bound forms. The tertiary structures of D1 and D2 are very similar, but doubly phosphorylated CD3zeta immunoreceptor tyrosine-based activation motif peptide binds only the D1 active site. The D2 "active site" deviates from the other active sites significantly to the extent that excludes any possibility of catalytic activity. The relative orientation of D1 and D2 is very similar to that observed in leukocyte common antigen-related protein with both active sites in an open conformation and is restrained through an extensive network of hydrophobic interactions, hydrogen bonds, and salt bridges. This crystal structure is incompatible with the wedge model previously suggested for CD45 regulation.
Disease
Known diseases associated with this structure: Hepatitic C virus, susceptibility to OMIM:[151460], Multiple sclerosis, susceptibility to OMIM:[151460], Severe combined immunodeficiency due to PTPRC deficiency OMIM:[151460]
About this Structure
1YGU is a Protein complex structure of sequences from Homo sapiens. Active as Protein-tyrosine-phosphatase, with EC number 3.1.3.48 Full crystallographic information is available from OCA.
Reference
Structural basis for the function and regulation of the receptor protein tyrosine phosphatase CD45., Nam HJ, Poy F, Saito H, Frederick CA, J Exp Med. 2005 Feb 7;201(3):441-52. Epub 2005 Jan 31. PMID:15684325
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