PMID- 28364043
OWN - NLM
STAT- MEDLINE
DCOM- 20170609
LR  - 20210205
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 292
IP  - 22
DP  - 2017 Jun 2
TI  - Unraveling the structural basis for the unusually rich association of human 
      leukocyte antigen DQ2.5 with class-II-associated invariant chain peptides.
PG  - 9218-9228
LID - 10.1074/jbc.M117.785139 [doi]
AB  - Human leukocyte antigen (HLA)-DQ2.5 (DQA1*05/DQB1*02) is a class-II major 
      histocompatibility complex protein associated with both type 1 diabetes and 
      celiac disease. One unusual feature of DQ2.5 is its high class-II-associated 
      invariant chain peptide (CLIP) content. Moreover, HLA-DQ2.5 preferentially binds 
      the non-canonical CLIP2 over the canonical CLIP1. To better understand the 
      structural basis of HLA-DQ2.5's unusual CLIP association characteristics, better 
      insight into the HLA-DQ2.5.CLIP complex structures is required. To this end, we 
      determined the X-ray crystal structure of the HLA-DQ2.5. CLIP1 and 
      HLA-DQ2.5.CLIP2 complexes at 2.73 and 2.20 A, respectively. We found that 
      HLA-DQ2.5 has an unusually large P4 pocket and a positively charged 
      peptide-binding groove that together promote preferential binding of CLIP2 over 
      CLIP1. An alpha9-alpha22-alpha24-alpha31-beta86-beta90 hydrogen bond network located at the bottom of 
      the peptide-binding groove, spanning from the P1 to P4 pockets, renders the 
      residues in this region relatively immobile. This hydrogen bond network, along 
      with a deletion mutation at alpha53, may lead to HLA-DM insensitivity in HLA-DQ2.5. A 
      molecular dynamics simulation experiment reported here and recent biochemical 
      studies by others support this hypothesis. The diminished HLA-DM sensitivity is 
      the likely reason for the CLIP-rich phenotype of HLA-DQ2.5.
CI  - (c) 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
FAU - Nguyen, Thanh-Binh
AU  - Nguyen TB
AD  - the Bioinformatics Institute, Singapore 138671, Singapore.
AD  - the Department of Biological Sciences, National University of Singapore, 
      Singapore 117543, Singapore.
FAU - Jayaraman, Priya
AU  - Jayaraman P
AD  - the Department of Biological Sciences, National University of Singapore, 
      Singapore 117543, Singapore.
FAU - Bergseng, Elin
AU  - Bergseng E
AD  - the Centre for Immune Regulation and Department of Immunology, University of Oslo 
      and Oslo University Hospital, N-0372 Oslo, Norway.
FAU - Madhusudhan, M S
AU  - Madhusudhan MS
AD  - the Bioinformatics Institute, Singapore 138671, Singapore.
AD  - the Indian Institute of Science Education and Research, Pune 411008, India, and.
FAU - Kim, Chu-Young
AU  - Kim CY
AD  - From the Department of Chemistry and ckim7@utep.edu.
AD  - School of Pharmacy, University of Texas at El Paso, El Paso, Texas 79968.
AD  - Synthetic Biology for Clinical and Technological Innovation, Life Sciences 
      Institute, National University of Singapore, 117456 Singapore, Singapore.
FAU - Sollid, Ludvig M
AU  - Sollid LM
AD  - the Centre for Immune Regulation and Department of Immunology, University of Oslo 
      and Oslo University Hospital, N-0372 Oslo, Norway l.m.sollid@medisin.uio.no.
LA  - eng
SI  - PDB/1IIE
SI  - PDB/5KSU
SI  - PDB/5KSV
SI  - PDB/1S9V
SI  - PDB/4OZF
SI  - PDB/4OZG
SI  - PDB/4OZH
SI  - PDB/3PDO
SI  - PDB/1A6A
SI  - PDB/1MUJ
SI  - PDB/1H15
SI  - PDB/2SEB
SI  - PDB/2Q6W
SI  - PDB/2NNA
SI  - PDB/2IAD
SI  - PDB/3MBE
SI  - PDB/1D9K
SI  - PDB/3QIU
SI  - PDB/4FQX
GR  - P41 GM103393/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170331
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ alpha-Chains)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQ2 antigen)
RN  - 0 (HLA-DQA1 antigen)
RN  - 0 (HLA-DQB1 antigen)
RN  - 0 (Peptides)
SB  - IM
MH  - Binding Sites
MH  - HLA-DQ Antigens/*chemistry/genetics
MH  - HLA-DQ alpha-Chains/*chemistry/genetics
MH  - HLA-DQ beta-Chains/*chemistry/genetics
MH  - Humans
MH  - *Molecular Dynamics Simulation
MH  - Peptides/*chemistry/genetics
PMC - PMC5454103
OTO - NOTNLM
OT  - HLA-DM
OT  - HLA-DQ
OT  - X-ray crystallography
OT  - autoimmune disease
OT  - celiac disease
OT  - major histocompatibility complex (MHC)
OT  - molecular dynamics
OT  - type 1 diabetes
COIS- The authors declare that they have no conflicts of interest with the contents of 
      this article
EDAT- 2017/04/02 06:00
MHDA- 2017/06/10 06:00
PMCR- 2018/06/02
CRDT- 2017/04/02 06:00
PHST- 2017/03/07 00:00 [received]
PHST- 2017/03/28 00:00 [revised]
PHST- 2017/04/02 06:00 [pubmed]
PHST- 2017/06/10 06:00 [medline]
PHST- 2017/04/02 06:00 [entrez]
PHST- 2018/06/02 00:00 [pmc-release]
AID - S0021-9258(20)42719-X [pii]
AID - M117.785139 [pii]
AID - 10.1074/jbc.M117.785139 [doi]
PST - ppublish
SO  - J Biol Chem. 2017 Jun 2;292(22):9218-9228. doi: 10.1074/jbc.M117.785139. Epub 
      2017 Mar 31.