PDBsum entry 3c5j

Membrane protein

PDB id: 3c5j

Contents

Protein chains

178 a.a. *

182 a.a. *

13 a.a. *

Ligands

NAG ×2

SO4

Waters ×454

* Residue conservation analysis

PDB id:

3c5j

Name:

Membrane protein

Title:

Crystal structure of hla dr52c

Structure:

Hla class ii histocompatibility antigen, dr alpha chain. Chain: a. Fragment: unp residues 25-206. Synonym: mhc class ii antigen dra. Engineered: yes. Mhc class ii antigen. Chain: b. Fragment: unp residues 30-219. Engineered: yes.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-dra, hla-dra1. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gene: hla-drb3. Gene: eef1a2, eef1al, stn.

Resolution:

1.80Å R-factor: 0.202 R-free: 0.227

Authors:

S.Dai,J.W.Kappler

Key ref:

S.Dai et al. (2008). The structure of HLA-DR52c: comparison to other HLA-DRB3 alleles. Proc Natl Acad Sci U S A, 105, 11893-11897. PubMed id: 18697946 DOI: 10.1073/pnas.0805810105

Date:

31-Jan-08 Release date: 05-Aug-08

Protein chain

P01903  (DRA_HUMAN) -  HLA class II histocompatibility antigen, DR alpha chain from Homo sapiens

Seq: 254 a.a.

Struc: 178 a.a.

Protein chain

B8YAC7  (B8YAC7_HUMAN) -  MHC class II antigen (Fragment) from Homo sapiens

Seq: 183 a.a.

Struc: 182 a.a.

Protein chain

Q05639  (EF1A2_HUMAN) -  Elongation factor 1-alpha 2 from Homo sapiens

Seq: 463 a.a.

Struc: 13 a.a.

DOI no: 10.1073/pnas.0805810105

Proc Natl Acad Sci U S A 105:11893-11897 (2008)

PubMed id: 18697946

The structure of HLA-DR52c: comparison to other HLA-DRB3 alleles.

S.Dai, F.Crawford, P.Marrack, J.W.Kappler.

ABSTRACT

Class II major histocompatibility complex (MHCII) molecules present antigens to CD4(+) T cells. In addition to the most commonly studied human MHCII isotype, HLA-DR, whose beta chain is encoded by the HLA-DRB1 locus, several other isotypes that use the same alpha chain but have beta chains encoded by other genes. These other DR molecules also are expressed in antigen-presenting cells and are known to participate in peptide presentation to T cells and to be recognized as alloantigens by other T cells. Like some of the HLA-DRB1 alleles, several of these alternate DR molecules have been associated with specific autoimmune diseases and T cell hypersensitivity. Here we present the structure of an HLA-DR molecule (DR52c) containing one of these alternate beta chains (HLA-DRB3*0301) bound to a self-peptide derived from the Tu elongation factor. The molecule shares structurally conserved elements with other MHC class II molecules but has some unique features in the peptide-binding groove. Comparison of the three major HLA-DBR3 alleles (DR52a, b, and c) suggests that they were derived from one another by recombination events that scrambled the four major peptide-binding pockets at peptide positions 1, 4, 6, and 9 but left virtually no polymorphisms elsewhere in the molecules.

Selected figure(s)

Figure 2.
DR52c peptide-binding pockets. The α1 domain is shown in cyan; the β1 domain, in magenta. The Tu peptide is colored as in Fig. 1. Water molecules deep in the pockets (shown as red balls) are labeled W0, W1, and W2. (A) Side view of the solvent-accessible surface (probe radius of 1.4 Å) of the peptide-binding groove. The peptide is shown as a wire frame. The β1 helix has been partially cut away for clarity. (B) Top view of the solvent-accessible surfaces of the four peptide amino acid-binding pockets (P1, P4, P6, and P9) of DR52c, showing only the side chains of the four bound residues.

Figure 3.
The hydrogen-bonding network in the P4 and P6 pockets. The predicted hydrogen bonds among the atoms are shown as green dotted lines. The water molecules are shown as red balls. White, peptide carbon; cyan, α chain carbon; magenta, β chain carbon; blue, nitrogen; red, oxygen. (A) Details of the hydrogen bond interactions between P4 Asn and the DR52c. The side chains of Gln α9, Ser β13, Glu β28, Lys β72, and Gln β74 are shown as sticks. Three ordered water molecules are labeled W3, W4, and W5. (B) Details of the peptide-binding pocket P6. The side chains of P6 Pro and DR52c Asp α66, Asn α69, Glu β9, Tyr β30 and Leu β11 are shown as sticks. Two ordered water molecules are labeled W1 and W2. (C) A hypothetical network in the P6 pocket occupied by Arg.

Figures were selected by an automated process.