PDBsum entry 4p4k

Immune system

PDB id: 4p4k

Contents

Protein chains

178 a.a.

199 a.a.

204 a.a.

241 a.a.

Ligands

NAG ×5

Metals

0BE ×2

_NA ×2

Waters ×330

PDB id:

4p4k

Name:

Immune system

Title:

Structural basis of chronic beryllium disease: bridging the gap between allergic hypersensitivity and auto immunity

Structure:

Hla class ii histocompatibility antigen, dp alpha 1 chain. Chain: a, e. Fragment: unp residues 32-214. Synonym: dp(w3),dp(w4),hla-sb alpha chain,mhc class ii dp3-alpha,mhc class ii dpa1. Engineered: yes. Mim2 peptide,hla class ii histocompatibility antigen, dp beta 1 chain. Chain: b, f.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-dpa1, hla-dp1a, hlasb. Expressed in: unidentified baculovirus. Expression_system_taxid: 10469. Gene: hla-dpb1, hla-dp1b. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.80Å R-factor: 0.206 R-free: 0.252

Authors:

G.M.Clayton,F.Crawford,J.W.Kappler

Key ref:

G.M.Clayton et al. (2014). Structural basis of chronic beryllium disease: linking allergic hypersensitivity and autoimmunity. Cell, 158, 132-142. PubMed id: 24995984 DOI: 10.1016/j.cell.2014.04.048

Date:

12-Mar-14 Release date: 16-Jul-14

Protein chains

P20036  (DPA1_HUMAN) -  HLA class II histocompatibility antigen, DP alpha 1 chain from Homo sapiens

Seq: 260 a.a.

Struc: 178 a.a.

Protein chains

P04440  (DPB1_HUMAN) -  HLA class II histocompatibility antigen, DP beta 1 chain from Homo sapiens

Seq: 258 a.a.

Struc: 199 a.a.*

Protein chains

P01848  (TCA_HUMAN) -  T cell receptor alpha chain constant from Homo sapiens

Seq: 140 a.a.

Struc: 204 a.a.*

Protein chains

A0A5B9  (TRBC2_HUMAN) -  T cell receptor beta constant 2 from Homo sapiens

Seq: 178 a.a.

Struc: 241 a.a.*

* PDB and UniProt seqs differ at 21 residue positions (black crosses)

DOI no: 10.1016/j.cell.2014.04.048

Cell 158:132-142 (2014)

PubMed id: 24995984

Structural basis of chronic beryllium disease: linking allergic hypersensitivity and autoimmunity.

G.M.Clayton, Y.Wang, F.Crawford, A.Novikov, B.T.Wimberly, J.S.Kieft, M.T.Falta, N.A.Bowerman, P.Marrack, A.P.Fontenot, S.Dai, J.W.Kappler.

ABSTRACT

T-cell-mediated hypersensitivity to metal cations is common in humans. How the T cell antigen receptor (TCR) recognizes these cations bound to a major histocompatibility complex (MHC) protein and self-peptide is unknown. Individuals carrying the MHCII allele, HLA-DP2, are at risk for chronic beryllium disease (CBD), a debilitating inflammatory lung condition caused by the reaction of CD4 T cells to inhaled beryllium. Here, we show that the T cell ligand is created when a Be(2+) cation becomes buried in an HLA-DP2/peptide complex, where it is coordinated by both MHC and peptide acidic amino acids. Surprisingly, the TCR does not interact with the Be(2+) itself, but rather with surface changes induced by the firmly bound Be(2+) and an accompanying Na(+) cation. Thus, CBD, by creating a new antigen by indirectly modifying the structure of preexisting self MHC-peptide complex, lies on the border between allergic hypersensitivity and autoimmunity.