PMID- 22343629
OWN - NLM
STAT- MEDLINE
DCOM- 20120606
LR  - 20211021
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 287
IP  - 15
DP  - 2012 Apr 6
TI  - The energetic basis underpinning T-cell receptor recognition of a super-bulged 
      peptide bound to a major histocompatibility complex class I molecule.
PG  - 12267-76
LID - 10.1074/jbc.M112.344689 [doi]
AB  - Although the major histocompatibility complex class I (MHC-I) molecules typically 
      bind short peptide (p) fragments (8-10 amino acids in length), longer, "bulged" 
      peptides are often be presented by MHC-I. Such bulged pMHC-I complexes represent 
      challenges for T-cell receptor (TCR) ligation, although the general principles 
      underscoring the interaction between TCRs and bulged pMHC-I complexes are 
      unclear. To address this, we have explored the energetic basis of how an 
      immunodominant TCR (termed SB27) binds to a 13-amino acid viral peptide 
      (LPEPLPQGQLTAY) complexed to human leukocyte antigen (HLA) B*3508. Using the 
      crystal structure of the SB27 TCR-HLA B*3508(LPEP) complex as a guide, we 
      undertook a comprehensive alanine-scanning mutagenesis approach at the TCR-pMHC-I 
      interface and examined the effect of the mutations by biophysical (affinity 
      measurements) and cellular approaches (tetramer staining). Although the 
      structural footprint on HLA B*3508 was small, the energetic footprint was even 
      smaller in that only two HLA B*3508 residues were critical for the TCR 
      interaction. Instead, the energetic basis of this TCR-pMHC-I interaction was 
      attributed to peptide-mediated interactions in which the complementarity 
      determining region 3alpha and germline-encoded complementarity determining region 1beta 
      loops of the SB27 TCR played the principal role. Our findings highlight the 
      peptide-centricity of TCR ligation toward a bulged pMHC-I complex.
FAU - Liu, Yu Chih
AU  - Liu YC
AD  - Department of Biochemistry and Molecular Biology, Monash University, Clayton, 
      3800, Australia.
FAU - Chen, Zhenjun
AU  - Chen Z
FAU - Burrows, Scott R
AU  - Burrows SR
FAU - Purcell, Anthony W
AU  - Purcell AW
FAU - McCluskey, James
AU  - McCluskey J
FAU - Rossjohn, Jamie
AU  - Rossjohn J
FAU - Gras, Stephanie
AU  - Gras S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120216
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (HLA-B35 Antigen)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Viral Proteins)
SB  - IM
MH  - Amino Acid Motifs
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Crystallography, X-Ray
MH  - HLA-B35 Antigen/*chemistry/genetics
MH  - Humans
MH  - Kinetics
MH  - Models, Molecular
MH  - Mutagenesis, Site-Directed
MH  - Peptides/*chemistry
MH  - Protein Binding
MH  - Protein Stability
MH  - Protein Structure, Quaternary
MH  - Protein Structure, Tertiary
MH  - Receptors, Antigen, T-Cell/*chemistry
MH  - Surface Plasmon Resonance
MH  - Surface Properties
MH  - Thermodynamics
MH  - Viral Proteins/chemistry
PMC - PMC3320977
EDAT- 2012/02/22 06:00
MHDA- 2012/06/07 06:00
PMCR- 2013/04/06
CRDT- 2012/02/21 06:00
PHST- 2012/02/21 06:00 [entrez]
PHST- 2012/02/22 06:00 [pubmed]
PHST- 2012/06/07 06:00 [medline]
PHST- 2013/04/06 00:00 [pmc-release]
AID - S0021-9258(20)53155-4 [pii]
AID - M112.344689 [pii]
AID - 10.1074/jbc.M112.344689 [doi]
PST - ppublish
SO  - J Biol Chem. 2012 Apr 6;287(15):12267-76. doi: 10.1074/jbc.M112.344689. Epub 2012 
      Feb 16.