5IB3

Crystal structure of HLA-B*27:05 complexed with the self-peptide pVIPR and Copper

Summary for 5IB3

• Entry DOI: 10.2210/pdb5ib3/pdb
• Descriptor: HLA class I histocompatibility antigen, B-27 alpha chain, Beta-2-microglobulin, Vasoactive intestinal polypeptide receptor 1, ... (6 entities in total)
• Functional Keywords: immune system-complex, immune system, mhc major histocompatibility complex), hla- b*2705
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 45518.49

Authors

Janke, R.,Ballaschk, M.,Schmieder, P.,Uchanska-Ziegler, B.,Ziegler, A.,Loll, B. (deposition date: 2016-02-22, release date: 2017-02-01, Last modification date: 2024-11-06)

Primary citation

Driller, R.,Ballaschk, M.,Schmieder, P.,Uchanska-Ziegler, B.,Ziegler, A.,Loll, B.
Metal-triggered conformational reorientation of a self-peptide bound to a disease-associated HLA-B*27 subtype.
J.Biol.Chem., 2019

PubMed Abstract: Conformational changes of major histocompatibility complex (MHC) antigens have the potential to be recognized by T cells and may arise from polymorphic variation of the MHC molecule, the binding of modifying ligands, or both. Here, we investigated whether metal ions could affect allele-dependent structural variation of the two minimally distinct human leukocyte antigen (HLA)-B*27:05 and HLA-B*27:09 subtypes, which exhibit differential association with the rheumatic disease ankylosing spondylitis (AS). We employed NMR spectroscopy and X-ray crystallography coupled with ensemble refinement to study the AS-associated HLA-B*27:05 subtype and the AS-nonassociated HLA-B* 27:09 in complex with the self-peptide pVIPR (RRKWRRWHL). Both techniques revealed that pVIPR exhibits a higher degree of flexibility when complexed with HLA-B*27:05 than with HLA-B*27:09. Furthermore, we found that the binding of the metal ion Cu or Ni, but not Mn, Zn, or Hg, affects the structure of a pVIPR-bound HLA-B*27 molecule in a subtype-dependent manner. In HLA-B*27:05, the metals triggered conformational reorientations of pVIPR, but no such structural changes were observed in the HLA-B*27:09 subtype, with or without bound metal ion. These observations provide the first demonstration that not only major histocompatibility complex class II, but also class I, molecules can undergo metal ion-induced conformational alterations. Our findings suggest that metals may have a role in triggering rheumatic diseases such as AS and also have implications for the molecular basis of metal-induced hypersensitivities and allergies.

PubMed: 31296658
DOI: 10.1074/jbc.RA119.008937

Experimental method

X-RAY DIFFRACTION (1.91 Å)