PMID- 28278760
OWN - NLM
STAT- MEDLINE
DCOM- 20190109
LR  - 20190109
IS  - 1538-0254 (Electronic)
IS  - 0739-1102 (Linking)
VI  - 36
IP  - 3
DP  - 2018 Feb
TI  - Computational characterization of residue couplings and micropolymorphism-induced 
      changes in the dynamics of two differentially disease-associated human MHC 
      class-I alleles.
PG  - 724-740
LID - 10.1080/07391102.2017.1295884 [doi]
AB  - Human major histocompatibility complex class I (MHC I) - or human leukocyte 
      antigen (HLA) - proteins present intracellularly processed peptides to cytotoxic 
      T lymphocytes in the adaptive immune response to pathogens. A high level of 
      polymorphism in human MHC I proteins defines the peptide-binding specificity of 
      thousands of different MHC alleles. However, polymorphism as well as the peptide 
      ligand can also affect the global dynamics of the complex. In this study, we 
      conducted classical molecular dynamics simulations of two HLA alleles, the 
      ankylosing spondylitis (AS) associated/tapasin-dependent HLA-B*27:05 and 
      nondisease-associated/tapasin-independent HLA-B*27:09, both in peptide-free forms 
      as well as complex with four different peptides ligands. Our results indicate 
      that in peptide-free form, the single amino acid substitution distinguishing the 
      two alleles (D116H), leads to a weaker dynamic coupling of residues in the 
      tapasin-dependent HLA-B*27:05. In peptide-bound form, several residues of the 
      binding-groove, mostly in A and B pockets, show hinge-like behavior in the global 
      motion of the MHC. Moreover, allele-dependent changes are shown in residue 
      interactions, affecting the B-pocket as well as the beta-2-microglobulin 
      (beta2m)-facing residues of the HLA chain.
FAU - Sercinoglu, Onur
AU  - Sercinoglu O
AD  - a Department of Bioengineering , Institute of Pure and Applied Sciences, Marmara 
      University , Istanbul , Turkey.
AD  - b Faculty of Engineering, Department of Bioengineering , Marmara University , 
      Istanbul , Turkey.
FAU - Ozbek, Pemra
AU  - Ozbek P
AD  - b Faculty of Engineering, Department of Bioengineering , Marmara University , 
      Istanbul , Turkey.
LA  - eng
PT  - Journal Article
DEP - 20170301
PL  - England
TA  - J Biomol Struct Dyn
JT  - Journal of biomolecular structure & dynamics
JID - 8404176
RN  - 0 (HLA-B*27:05 antigen)
RN  - 0 (HLA-B*27:09 antigen)
RN  - 0 (HLA-B27 Antigen)
RN  - 0 (Ligands)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Peptides)
RN  - 0 (tapasin)
SB  - IM
MH  - Alleles
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution/genetics
MH  - Binding Sites
MH  - Computational Biology
MH  - HLA-B27 Antigen/chemistry/*genetics/immunology
MH  - Humans
MH  - Ligands
MH  - Membrane Transport Proteins/chemistry
MH  - Molecular Dynamics Simulation
MH  - Peptides/chemistry/genetics/immunology
MH  - Polymorphism, Genetic
MH  - Protein Binding
MH  - *Protein Conformation
MH  - Spondylitis, Ankylosing/*genetics/immunology/pathology
OTO - NOTNLM
OT  - HLA-B27
OT  - Tapasin dependency
OT  - allostery
OT  - ankylosing spondylitis
OT  - global dynamics
OT  - human leukocyte antigens
OT  - major histocompatibility complex class I
OT  - molecular dynamics
EDAT- 2017/03/11 06:00
MHDA- 2019/01/10 06:00
CRDT- 2017/03/11 06:00
PHST- 2017/03/11 06:00 [pubmed]
PHST- 2019/01/10 06:00 [medline]
PHST- 2017/03/11 06:00 [entrez]
AID - 10.1080/07391102.2017.1295884 [doi]
PST - ppublish
SO  - J Biomol Struct Dyn. 2018 Feb;36(3):724-740. doi: 10.1080/07391102.2017.1295884. 
      Epub 2017 Mar 1.