CRYSTAL STRUCTURE OF THE HUMAN CD4 N-TERMINAL TWO DOMAIN FRAGMENT COMPLEXED TO A CLASS II MHC MOLECULE

File:1jl4.gif


1jl4, resolution 4.3Å

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OverviewOverview

The structural basis of the interaction between the CD4 coreceptor and a, class II major histocompatibility complex (MHC) is described. The crystal, structure of a complex containing the human CD4 N-terminal two-domain, fragment and the murine I-A(k) class II MHC molecule with associated, peptide (pMHCII) shows that only the "top corner" of the CD4 molecule, directly contacts pMHCII. The CD4 Phe-43 side chain extends into a, hydrophobic concavity formed by MHC residues from both alpha 2 and beta 2, domains. A ternary model of the CD4-pMHCII-T-cell receptor (TCR) reveals, that the complex appears V-shaped with the membrane-proximal pMHCII at the, apex. This configuration excludes a direct TCR-CD4 interaction and, suggests how TCR and CD4 signaling is coordinated around the antigenic, pMHCII complex. Human CD4 binds to HIV gp120 in a manner strikingly, similar to the way in which CD4 interacts with pMHCII. Additional contacts, between gp120 and CD4 give the CD4-gp120 complex a greater affinity. Thus, ligation of the viral envelope glycoprotein to CD4 occludes the, pMHCII-binding site on CD4, contributing to immunodeficiency.

About this StructureAbout this Structure

1JL4 is a Protein complex structure of sequences from Gallus gallus, Homo sapiens and Mus musculus. Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of the human CD4 N-terminal two-domain fragment complexed to a class II MHC molecule., Wang JH, Meijers R, Xiong Y, Liu JH, Sakihama T, Zhang R, Joachimiak A, Reinherz EL, Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10799-804. Epub 2001 Sep 4. PMID:11535811

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