PMID- 20810170
OWN - NLM
STAT- MEDLINE
DCOM- 20110103
LR  - 20121115
IS  - 1872-9142 (Electronic)
IS  - 0161-5890 (Linking)
VI  - 48
IP  - 1-3
DP  - 2010 Nov-Dec
TI  - The autoimmune TCR-Ob.2F3 can bind to MBP85-99/HLA-DR2 having an unconventional 
      mode as in TCR-Ob.1A12.
PG  - 314-20
LID - 10.1016/j.molimm.2010.07.010 [doi]
AB  - The generation of T cell receptor (TCR) sequence diversity can produce 
      'forbidden' clones able to recognize self-antigens. Here, the structure of the 
      complex between a myelin basic protein peptide (MBP85-99), human leukocyte 
      antigen (HLA)-DR2 (DRB1*1501/DRA) and TCR-Ob.2F3, the dominant autoimmune clone 
      obtained from a multiple sclerosis (MS) patient, has been determined using 
      structural docking simulation and dynamics in silico and compared to the 
      structure of TCR-Ob.1A12 complexes with the same MHC/peptide determined by X-ray 
      crystallography. The two TCRs differ by three amino acids in the CDR3 alpha and beta 
      loops. As the result different hydrogen bonds are formed between the two CDR3beta 
      loops and the peptide in the complexes of the simulated structures, with three 
      hydrogen bonds seen in the TCR-Ob.2F3 complex and five in the TCR-Ob.1A12 
      complex. The two TCRs, each located near the N-terminal end of the HLA-DR2 
      binding groove and both had an orthogonal binding axis but they deviated by about 
      10 degrees . Simulation methods, such as structural docking and molecular dynamics as 
      used here, provide an avenue to understand molecular binding mode efficiently and 
      more rapidly than obtaining multiple crystal structures when a large structural 
      database is already available.
CI  - Copyright (c) 2010 Elsevier Ltd. All rights reserved.
FAU - Kato, Zenichiro
AU  - Kato Z
AD  - Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, 
      MA 02193, USA. zenkato@mac.com
FAU - Stern, Joel N H
AU  - Stern JN
FAU - Nakamura, Hironori K
AU  - Nakamura HK
FAU - Miyashita, Naoyuki
AU  - Miyashita N
FAU - Kuwata, Kazuo
AU  - Kuwata K
FAU - Kondo, Naomi
AU  - Kondo N
FAU - Strominger, Jack L
AU  - Strominger JL
LA  - eng
GR  - R01 AI49524/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - Mol Immunol
JT  - Molecular immunology
JID - 7905289
RN  - 0 (Autoantigens)
RN  - 0 (HLA-DR2 Antigen)
RN  - 0 (Myelin Basic Protein)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (myelin basic protein 85-99)
SB  - IM
MH  - Autoantigens/*chemistry/immunology
MH  - Crystallography, X-Ray
MH  - HLA-DR2 Antigen/*chemistry/immunology
MH  - Humans
MH  - Imaging, Three-Dimensional/*methods
MH  - Models, Structural
MH  - Multiple Sclerosis/immunology
MH  - Myelin Basic Protein/*chemistry/immunology
MH  - Peptide Fragments/*chemistry/immunology
MH  - Protein Structure, Quaternary
MH  - Receptors, Antigen, T-Cell/*chemistry/immunology
EDAT- 2010/09/03 06:00
MHDA- 2011/01/05 06:00
CRDT- 2010/09/03 06:00
PHST- 2010/04/05 00:00 [received]
PHST- 2010/06/30 00:00 [revised]
PHST- 2010/07/18 00:00 [accepted]
PHST- 2010/09/03 06:00 [entrez]
PHST- 2010/09/03 06:00 [pubmed]
PHST- 2011/01/05 06:00 [medline]
AID - S0161-5890(10)00524-9 [pii]
AID - 10.1016/j.molimm.2010.07.010 [doi]
PST - ppublish
SO  - Mol Immunol. 2010 Nov-Dec;48(1-3):314-20. doi: 10.1016/j.molimm.2010.07.010.