PMID- 18178223
OWN - NLM
STAT- MEDLINE
DCOM- 20080219
LR  - 20080205
IS  - 1089-8638 (Electronic)
IS  - 0022-2836 (Linking)
VI  - 376
IP  - 3
DP  - 2008 Feb 22
TI  - HLA-B27 subtypes differentially associated with disease exhibit conformational 
      differences in solution.
PG  - 798-810
LID - 10.1016/j.jmb.2007.12.009 [doi]
AB  - Human leukocyte antigen (HLA) class I molecules consist of a heavy chain, 
      beta(2)-microglobulin, and a peptide that are noncovalently bound. Certain 
      HLA-B27 subtypes are associated with ankylosing spondylitis (such as HLA-B*2705), 
      whereas others (such as HLA-B*2709) are not. Both differ in only one residue 
      (Asp116 and His116, respectively) in the F pocket that accommodates the peptide 
      C-terminus. An isotope-edited IR spectroscopy study of these HLA-B27 subtypes 
      complexed with the self-peptide RRKWRRWHL was carried out, revealing that the 
      heavy chain is more flexible in the HLA-B*2705 than in the HLA-B*2709 subtype. In 
      agreement with these experimental data, molecular dynamics simulations showed an 
      increased flexibility of the HLA-B*2705 binding groove in comparison with that of 
      the HLA-B*2709 subtype. This difference correlates with an opening of the 
      HLA-B*2705 binding groove, accompanied by a partial detachment of the C-terminal 
      peptide anchor. These combined results demonstrate how the deeply embedded 
      polymorphic heavy-chain residue 116 influences the flexibility of the peptide 
      binding groove in a subtype-dependent manner, a feature that could also influence 
      the recognition of the HLA-B27 complexes by effector cells.
FAU - Fabian, Heinz
AU  - Fabian H
AD  - Robert Koch-Institut, P 25, Nordufer 20, D-13353 Berlin, Germany. fabianh@rki.de
FAU - Huser, Hans
AU  - Huser H
FAU - Narzi, Daniele
AU  - Narzi D
FAU - Misselwitz, Rolf
AU  - Misselwitz R
FAU - Loll, Bernhard
AU  - Loll B
FAU - Ziegler, Andreas
AU  - Ziegler A
FAU - Bockmann, Rainer A
AU  - Bockmann RA
FAU - Uchanska-Ziegler, Barbara
AU  - Uchanska-Ziegler B
FAU - Naumann, Dieter
AU  - Naumann D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071208
PL  - Netherlands
TA  - J Mol Biol
JT  - Journal of molecular biology
JID - 2985088R
RN  - 0 (HLA-B27 Antigen)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, Vasoactive Intestinal Polypeptide, Type I)
RN  - 0 (VIPR1 protein, human)
RN  - 0 (beta 2-Microglobulin)
SB  - IM
MH  - Binding Sites
MH  - Crystallography, X-Ray
MH  - HLA-B27 Antigen/*chemistry/metabolism
MH  - Humans
MH  - Models, Molecular
MH  - Peptide Fragments/chemistry/metabolism
MH  - Protein Conformation
MH  - Receptors, Vasoactive Intestinal Polypeptide, Type I/chemistry/metabolism
MH  - Spectrophotometry, Infrared
MH  - Spondylitis, Ankylosing/*metabolism
MH  - Thermodynamics
MH  - beta 2-Microglobulin/chemistry
EDAT- 2008/01/08 09:00
MHDA- 2008/02/20 09:00
CRDT- 2008/01/08 09:00
PHST- 2007/08/24 00:00 [received]
PHST- 2007/11/23 00:00 [revised]
PHST- 2007/12/05 00:00 [accepted]
PHST- 2008/01/08 09:00 [pubmed]
PHST- 2008/02/20 09:00 [medline]
PHST- 2008/01/08 09:00 [entrez]
AID - S0022-2836(07)01615-4 [pii]
AID - 10.1016/j.jmb.2007.12.009 [doi]
PST - ppublish
SO  - J Mol Biol. 2008 Feb 22;376(3):798-810. doi: 10.1016/j.jmb.2007.12.009. Epub 2007 
      Dec 8.