PMID- 31296658
OWN - NLM
STAT- MEDLINE
DCOM- 20200331
LR  - 20210317
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 294
IP  - 36
DP  - 2019 Sep 6
TI  - Metal-triggered conformational reorientation of a self-peptide bound to a 
      disease-associated HLA-B*27 subtype.
PG  - 13269-13279
LID - S0021-9258(20)30383-5 [pii]
LID - 10.1074/jbc.RA119.008937 [doi]
AB  - 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(2+) or 
      Ni(2+), but not Mn(2+), Zn(2+), or Hg(2+), 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.
CI  - (c) 2019 Driller et al.
FAU - Driller, Ronja
AU  - Driller R
AD  - Institut fur Chemie/Biochemie, AG Strukturbiochemie, Freie Universitat Berlin, 
      Takustrasse 6, 14195 Berlin, Germany.
FAU - Ballaschk, Martin
AU  - Ballaschk M
AD  - Leibniz-Institut fur Molekulare Pharmakologie, Robert-Rossle-Strasse 10, 13125 
      Berlin, Germany.
FAU - Schmieder, Peter
AU  - Schmieder P
AD  - Leibniz-Institut fur Molekulare Pharmakologie, Robert-Rossle-Strasse 10, 13125 
      Berlin, Germany.
FAU - Uchanska-Ziegler, Barbara
AU  - Uchanska-Ziegler B
AD  - Institut fur Immungenetik, Charite-Universitatsmedizin Berlin, Freie Universitat 
      Berlin, Thielallee 73, 14195 Berlin, Germany; Ziegler Biosolutions, Fahrgasse 5, 
      79761 Waldshut-Tiengen, Germany.
FAU - Ziegler, Andreas
AU  - Ziegler A
AD  - Ziegler Biosolutions, Fahrgasse 5, 79761 Waldshut-Tiengen, Germany. Electronic 
      address: ziegler-biosolutions@gmx.de.
FAU - Loll, Bernhard
AU  - Loll B
AD  - Institut fur Chemie/Biochemie, AG Strukturbiochemie, Freie Universitat Berlin, 
      Takustrasse 6, 14195 Berlin, Germany; MoloX GmbH, Takustrasse 6, 14195 Berlin, 
      Germany. Electronic address: loll@chemie.fu-berlin.de.
LA  - eng
SI  - PDB/5IB1
SI  - PDB/5IB2
SI  - PDB/5IB3
SI  - PDB/5IB4
SI  - PDB/5IB5
SI  - PDB/1OF2
SI  - PDB/1OGT
SI  - PDB/1UXS
SI  - PDB/3B6S
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190711
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (HLA-B27 Antigen)
RN  - 0 (Metals, Heavy)
RN  - 0 (Organometallic Compounds)
RN  - 0 (Peptides)
SB  - IM
MH  - Crystallography, X-Ray
MH  - HLA-B27 Antigen/*chemistry/immunology
MH  - Humans
MH  - Metals, Heavy/*chemistry/immunology
MH  - Models, Molecular
MH  - Molecular Conformation
MH  - Organometallic Compounds/*chemistry/immunology
MH  - Peptides/*chemistry/immunology
PMC - PMC6737219
OTO - NOTNLM
OT  - HLA-B*27
OT  - NMR spectroscopy
OT  - X-ray crystallography
OT  - ankylosing spondylitis
OT  - autoimmune disease
OT  - autoimmunity
OT  - conformational change
OT  - crystal structure
OT  - ensemble refinement
OT  - hypersensitivity
OT  - major histocompatibility complex (MHC)
OT  - nuclear magnetic resonance (NMR)
OT  - peptide dynamics
COIS- The authors declare that they have no conflicts of interest with the contents of 
      this article
EDAT- 2019/07/13 06:00
MHDA- 2020/04/01 06:00
PMCR- 2020/09/06
CRDT- 2019/07/13 06:00
PHST- 2019/04/19 00:00 [received]
PHST- 2019/07/08 00:00 [revised]
PHST- 2019/07/13 06:00 [pubmed]
PHST- 2020/04/01 06:00 [medline]
PHST- 2019/07/13 06:00 [entrez]
PHST- 2020/09/06 00:00 [pmc-release]
AID - S0021-9258(20)30383-5 [pii]
AID - RA119.008937 [pii]
AID - 10.1074/jbc.RA119.008937 [doi]
PST - ppublish
SO  - J Biol Chem. 2019 Sep 6;294(36):13269-13279. doi: 10.1074/jbc.RA119.008937. Epub 
      2019 Jul 11.