1JL4

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

Summary for 1JL4

• Entry DOI: 10.2210/pdb1jl4/pdb
• Related: 1G9M 1IAK 1WIO 3CD4
• Descriptor: H-2 CLASS II HISTOCOMPATIBILITY ANTIGEN, A-K ALPHA CHAIN, H-2 CLASS II HISTOCOMPATIBILITY ANTIGEN, A-K BETA CHAIN, OVOTRANSFERRIN, ... (4 entities in total)
• Functional Keywords: protein-protein complex, immune system
• Biological source: Mus musculus (house mouse); More
• Cellular location: Membrane ; Single-pass type I membrane protein : P01910 P06343; Secreted: P02789; Cell membrane ; Single-pass type I membrane protein : P01730
• Total number of polymer chains: 4
• Total formula weight: 63743.58

Authors

Wang, J.-H.,Meijers, R.,Reinherz, E.L. (deposition date: 2001-07-15, release date: 2001-09-19, Last modification date: 2024-11-20)

Primary citation

Wang, J.H.,Meijers, R.,Xiong, Y.,Liu, J.H.,Sakihama, T.,Zhang, R.,Joachimiak, A.,Reinherz, E.L.
Crystal structure of the human CD4 N-terminal two-domain fragment complexed to a class II MHC molecule.
Proc.Natl.Acad.Sci.USA, 98:10799-10804, 2001

PubMed Abstract: 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.

PubMed: 11535811
DOI: 10.1073/pnas.191124098

Experimental method

X-RAY DIFFRACTION (4.3 Å)