PDBsum entry 1jl4

Immune system

PDB id: 1jl4

Contents

Protein chains

178 a.a. *

185 a.a. *

16 a.a. *

178 a.a. *

* Residue conservation analysis

PDB id:

1jl4

Name:

Immune system

Title:

Crystal structure of the human cd4 n-terminal two domain fragment complexed to a class ii mhc molecule

Structure:

H-2 class ii histocompatibility antigen, a-k alpha chain. Chain: a. Engineered: yes. H-2 class ii histocompatibility antigen, a-k beta chain. Chain: b. Engineered: yes. Ovotransferrin. Chain: c. Synonym: conalbumin.

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Gallus gallus. Chicken. Organism_taxid: 9031. Expressed in: gallus gallus.

Biol. unit:

Tetramer (from PQS)

Resolution:

4.30Å R-factor: 0.428 R-free: 0.453

Authors:

J.-H.Wang,R.Meijers,E.L.Reinherz

Key ref:

J.H.Wang et al. (2001). Crystal structure of the human CD4 N-terminal two-domain fragment complexed to a class II MHC molecule. Proc Natl Acad Sci U S A, 98, 10799-10804. PubMed id: 11535811 DOI: 10.1073/pnas.191124098

Date:

15-Jul-01 Release date: 19-Sep-01

Protein chain

P01910  (HA2K_MOUSE) -  H-2 class II histocompatibility antigen, A-K alpha chain from Mus musculus

Seq: 256 a.a.

Struc: 178 a.a.

Protein chain

P06343  (HB2K_MOUSE) -  H-2 class II histocompatibility antigen, A-K beta chain from Mus musculus

Seq: 263 a.a.

Struc: 185 a.a.*

Protein chain

P02789  (TRFE_CHICK) -  Ovotransferrin from Gallus gallus

Seq: 705 a.a.

Struc: 16 a.a.*

Protein chain

P01730  (CD4_HUMAN) -  T-cell surface glycoprotein CD4 from Homo sapiens

Seq: 458 a.a.

Struc: 178 a.a.

* PDB and UniProt seqs differ at 6 residue positions (black crosses)

DOI no: 10.1073/pnas.191124098

Proc Natl Acad Sci U S A 98:10799-10804 (2001)

PubMed id: 11535811

Crystal structure of the human CD4 N-terminal two-domain fragment complexed to a class II MHC molecule.

J.H.Wang, R.Meijers, Y.Xiong, J.H.Liu, T.Sakihama, R.Zhang, A.Joachimiak, E.L.Reinherz.

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.

Selected figure(s)

Figure 1.
Fig. 1. Ribbon diagram of the CD4-pMHCII complex. The murine I-A^k MHC class II molecule with a CA peptide (green) bound to the antigen-presenting platform interacts with hCD4 (cyan) through both the 2 (red) and the 2 (yellow) domains of pMHCII and domain 1 (D1) of hCD4. Residues Lys-35, Phe-43, Lys-46, and Arg-59 on CD4 D1 essential for binding are highlighted. The CD loop (delineated with an arrow) on the 2 domain of the I-A^k molecule is shown to have no direct interactions with CD4. Note also how CD4 D2 (unlabeled, cyan) makes no contact to pMHCII. All the figures were prepared with MOLSCRIPT (46) and RASTER 3D (47).

Figure 4.
Fig. 4. Molecular mimicry of gp120 binding to CD4 relative to MHC class II. (A) The CD4 D1D2-gp120 complex (ref. 42, with Fab not included for clarity) is shown in similar orientation to the complex of CD4 D1D2/I-A^k in Fig. 1. The interactions that are in common are displayed in the box, which shows the Phe-43 inserted in a hydrophobic pocket involving gp120 15 and 23, the formation of an antiparallel mini- -sheet between the C" strand of CD4 and 15 from gp120 as well as interactions between CD4 Arg-59 and the loop connecting 20 to 21 in gp120. Besides these core interactions, gp120 has additional contacts through the V1/V2 loop connecting the 2 and 3 strands, the D loop, and the V5 loop. (B) Overlay of CD4-CA/I-A^k and CD4-gp120 (42) complexes based on hCD4 D1 (blue and pink, respectively) with I-A^k in yellow and gp120 in red. Phe-43 and Arg-59 side chains are shown.

Figures were selected by an automated process.