PMID- 21902594
OWN - NLM
STAT- MEDLINE
DCOM- 20120309
LR  - 20220129
IS  - 1557-7716 (Electronic)
IS  - 1523-0864 (Linking)
VI  - 16
IP  - 1
DP  - 2012 Jan 1
TI  - The MHC Class I heavy chain structurally conserved cysteines 101 and 164 
      participate in HLA-B27 dimer formation.
PG  - 33-43
LID - 10.1089/ars.2010.3693 [doi]
AB  - AIMS: The human leukocyte antigen (HLA)-B27 is strongly associated with a group 
      of inflammatory arthritic disorders known as the spondyloarthropathies (SpAs). 
      The unusual biochemistry of HLA-B27 has been proposed to participate in disease 
      development, especially the enhanced ability of HLA-B27 to form several heavy 
      chain-dimer populations. HLA-B27 possesses three unpaired cysteine (C) residues 
      at position 67, 308, and 325, in addition to the four conserved cysteine residues 
      at p101, 164, 203, and 259. C67 was proposed to participate in dimer formation of 
      recombinant HLA-B27 protein and in vivo heavy chain-dimers. However, the 
      structurally conserved C164 was demonstrated to participate in endoplasmic 
      reticulum (ER) resident heavy chain-dimer formation. We therefore wanted to 
      determine whether these aggregates involve cysteines other than C164 and the 
      basis for the difference between the observed heavy chain-dimer species. RESULTS: 
      We determined that C164 and C101 can form distinct dimer structures and that the 
      heterogenous nature of heavy chain-dimer species is due to differences in both 
      redox status and conformation. Different HLA-B27 dimer populations can be found 
      in physiologically relevant cell types derived from HLA-B27-positive patients 
      with inflammatory arthritis. In addition, HLA-B27 dimer formation can be 
      correlated with cellular stress induction. INNOVATION: The use of both 
      mutagenesis and manipulating cellular redox environments demonstrates that 
      HLA-B27 dimerization requires both specific cysteine?cysteine interactions and 
      conformations with differing redox states. CONCLUSION: HLA-B27 heavy 
      chain-dimerization is a complex process and these findings provide an insight 
      into HLA-B27 misfolding and a potential contribution to inflammatory disease 
      development.
FAU - Lenart, Izabela
AU  - Lenart I
AD  - Department of Immunology and Molecular Pathology, Division of Infection and 
      Immunity/Centre of Rheumatology, University College London, United Kingdom.
FAU - Guiliano, David B
AU  - Guiliano DB
FAU - Burn, Garth
AU  - Burn G
FAU - Campbell, Elaine C
AU  - Campbell EC
FAU - Morley, Kenneth D
AU  - Morley KD
FAU - Fussell, Helen
AU  - Fussell H
FAU - Powis, Simon J
AU  - Powis SJ
FAU - Antoniou, Antony N
AU  - Antoniou AN
LA  - eng
GR  - 18440/ARC_/Arthritis Research UK/United Kingdom
GR  - 18440/VAC_/Versus Arthritis/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110915
PL  - United States
TA  - Antioxid Redox Signal
JT  - Antioxidants & redox signaling
JID - 100888899
RN  - 0 (Activating Transcription Factor 6)
RN  - 0 (HLA-B27 Antigen)
RN  - K848JZ4886 (Cysteine)
SB  - IM
MH  - Activating Transcription Factor 6/metabolism
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Line
MH  - Conserved Sequence
MH  - Cysteine/genetics/*metabolism
MH  - Endoplasmic Reticulum/metabolism
MH  - Endoplasmic Reticulum Stress
MH  - HLA-B27 Antigen/*chemistry/genetics/metabolism
MH  - Humans
MH  - Molecular Weight
MH  - Oxidation-Reduction
MH  - Protein Multimerization/physiology
MH  - Rats
EDAT- 2011/09/10 06:00
MHDA- 2012/03/10 06:00
CRDT- 2011/09/10 06:00
PHST- 2011/09/10 06:00 [entrez]
PHST- 2011/09/10 06:00 [pubmed]
PHST- 2012/03/10 06:00 [medline]
AID - 10.1089/ars.2010.3693 [doi]
PST - ppublish
SO  - Antioxid Redox Signal. 2012 Jan 1;16(1):33-43. doi: 10.1089/ars.2010.3693. Epub 
      2011 Sep 15.