1YGU

Crystal structure of the tandem phosphatase domains of RPTP CD45 with a pTyr peptide

Summary for 1YGU

• Entry DOI: 10.2210/pdb1ygu/pdb
• Related: 1YGR
• Descriptor: Leukocyte common antigen, Polyoma Middle T antigen (2 entities in total)
• Functional Keywords: cd45, protein tyrosine phosphatase, phosphotyrosine, polyoma middle t antigen, rptp, hydrolase
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P08575; Host membrane; Single-pass membrane protein (Potential): P03077
• Total number of polymer chains: 4
• Total formula weight: 144094.18

Authors

Nam, H.,Poy, F.,Saito, H.,Frederick, C.A. (deposition date: 2005-01-05, release date: 2005-02-22, Last modification date: 2024-10-16)

Primary citation

Nam, H.J.,Poy, F.,Saito, H.,Frederick, C.A.
Structural basis for the function and regulation of the receptor protein tyrosine phosphatase CD45.
J.Exp.Med., 201:441-452, 2005

PubMed Abstract: 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.

PubMed: 15684325
DOI: 10.1084/jem.20041890

Experimental method

X-RAY DIFFRACTION (2.9 Å)