6ATZ

HLA-DRB1*1402 in complex with citrullinated fibrinogen peptide

Summary for 6ATZ

• Entry DOI: 10.2210/pdb6atz/pdb
• Related: 6ATF 6ATI
• Descriptor: HLA class II histocompatibility antigen, DR alpha chain, MHC class II antigen, Fibrinogen beta chain, ... (6 entities in total)
• Functional Keywords: hla, mhc, citrulline, rheumatoid arthritis, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 88709.19

Authors

Ting, Y.T.,Scally, S.W.,Rossjohn, J. (deposition date: 2017-08-29, release date: 2017-09-20, Last modification date: 2024-11-06)

Primary citation

Scally, S.W.,Law, S.C.,Ting, Y.T.,Heemst, J.V.,Sokolove, J.,Deutsch, A.J.,Bridie Clemens, E.,Moustakas, A.K.,Papadopoulos, G.K.,Woude, D.V.,Smolik, I.,Hitchon, C.A.,Robinson, D.B.,Ferucci, E.D.,Bernstein, C.N.,Meng, X.,Anaparti, V.,Huizinga, T.,Kedzierska, K.,Reid, H.H.,Raychaudhuri, S.,Toes, R.E.,Rossjohn, J.,El-Gabalawy, H.,Thomas, R.
Molecular basis for increased susceptibility of Indigenous North Americans to seropositive rheumatoid arthritis.
Ann. Rheum. Dis., 76:1915-1923, 2017

PubMed Abstract: The pathogenetic mechanisms by which alleles are associated with anticitrullinated peptide antibody (ACPA)-positive rheumatoid arthritis (RA) are incompletely understood. RA high-risk alleles are known to share a common motif, the 'shared susceptibility epitope (SE)'. Here, the electropositive P4 pocket of HLA-DRB1 accommodates self-peptide residues containing citrulline but not arginine. HLA-DRB1 His/Phe13β stratifies with ACPA-positive RA, while His13βSer polymorphisms stratify with ACPA-negative RA and RA protection. Indigenous North American (INA) populations have high risk of early-onset ACPA-positive RA, whereby HLA-DRB1*04:04 and HLA-DRB1*14:02 are implicated as risk factors for RA in INA. However, HLA-DRB1*14:02 has a His13βSer polymorphism. Therefore, we aimed to verify this association and determine its molecular mechanism.

PubMed: 28801345
DOI: 10.1136/annrheumdis-2017-211300

Experimental method

X-RAY DIFFRACTION (2.7 Å)