PMID- 35667438
OWN - NLM
STAT- MEDLINE
DCOM- 20220726
LR  - 20220728
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 298
IP  - 7
DP  - 2022 Jul
TI  - Crystal structures of N-myristoylated lipopeptide-bound HLA class I complexes 
      indicate reorganization of B-pocket architecture upon ligand binding.
PG  - 102100
LID - S0021-9258(22)00541-5 [pii]
LID - 10.1016/j.jbc.2022.102100 [doi]
LID - 102100
AB  - Rhesus monkeys have evolved MHC-encoded class I allomorphs such as Mamu-B *098 
      that are capable of binding N-myristoylated short lipopeptides rather than 
      conventional long peptides; however, it remains unknown whether such 
      antigen-binding molecules exist in other species, including humans. We herein 
      demonstrate that human leukocyte antigen (HLA)-A *24:02 and HLA-C *14:02 proteins, 
      which are known to bind conventional long peptides, also have the potential to 
      bind N-myristoylated short lipopeptides. These HLA class I molecules shared a 
      serine at position 9 (Ser9) with Mamu-B *098, in contrast to most MHC class I 
      molecules that harbor a larger amino acid residue, such as tyrosine, at this 
      position. High resolution X-ray crystallographic analyses of lipopeptide-bound 
      HLA-A *24:02 and HLA-C *14:02 complexes indicated that Ser9 was at the bottom of 
      the B pocket with its small hydroxymethyl side chain directed away from the 
      B-pocket cavity, thereby contributing to the formation of a deep hydrophobic 
      cavity suitable for accommodating the long-chain fatty acid moiety of lipopeptide 
      ligands. Upon peptide binding, however, we found the hydrogen-bond network 
      involving Ser9 was reorganized, and the remodeled B pocket was able to capture 
      the second amino acid residue (P2) of peptide ligands. Apart from the B pocket, 
      virtually no marked alterations were observed for the A and F pockets upon 
      peptide and lipopeptide binding. Thus, we concluded that the structural 
      flexibility of the large B pocket of HLA-A *2402 and HLA-C *1402 primarily 
      accounted for their previously unrecognized capacity to bind such chemically 
      distinct ligands as conventional peptides and N-myristoylated lipopeptides.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Asa, Minori
AU  - Asa M
AD  - Laboratory of Cell Regulation, Institute for Life and Medical Sciences, Kyoto 
      University, Kyoto, Japan; Laboratory of Cell Regulation and Molecular Network, 
      Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
FAU - Morita, Daisuke
AU  - Morita D
AD  - Laboratory of Cell Regulation, Institute for Life and Medical Sciences, Kyoto 
      University, Kyoto, Japan; Laboratory of Cell Regulation and Molecular Network, 
      Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
FAU - Kuroha, Jin
AU  - Kuroha J
AD  - Laboratory of Cell Regulation, Institute for Life and Medical Sciences, Kyoto 
      University, Kyoto, Japan; Laboratory of Cell Regulation and Molecular Network, 
      Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
FAU - Mizutani, Tatsuaki
AU  - Mizutani T
AD  - Laboratory of Cell Regulation, Institute for Life and Medical Sciences, Kyoto 
      University, Kyoto, Japan; Laboratory of Cell Regulation and Molecular Network, 
      Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
FAU - Mori, Naoki
AU  - Mori N
AD  - Laboratory of Chemical Ecology, Division of Applied Life Sciences, Graduate 
      School of Agriculture, Kyoto University, Kyoto, Japan.
FAU - Mikami, Bunzo
AU  - Mikami B
AD  - Laboratory of Applied Structural Biology, Division of Applied Life Sciences, 
      Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
FAU - Sugita, Masahiko
AU  - Sugita M
AD  - Laboratory of Cell Regulation, Institute for Life and Medical Sciences, Kyoto 
      University, Kyoto, Japan; Laboratory of Cell Regulation and Molecular Network, 
      Graduate School of Biostudies, Kyoto University, Kyoto, Japan. Electronic 
      address: msugita@infront.kyoto-u.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20220603
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Amino Acids)
RN  - 0 (HLA-A*24:02 antigen)
RN  - 0 (HLA-A24 Antigen)
RN  - 0 (HLA-C Antigens)
RN  - 0 (HLA-C*14 antigen)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Ligands)
RN  - 0 (Lipopeptides)
SB  - IM
MH  - Amino Acids/chemistry
MH  - *HLA-A24 Antigen/chemistry
MH  - *HLA-C Antigens/chemistry
MH  - Histocompatibility Antigens Class I/chemistry
MH  - Humans
MH  - Ligands
MH  - *Lipopeptides
MH  - Protein Binding
PMC - PMC9243169
OTO - NOTNLM
OT  - antigen presentation
OT  - crystal structure
OT  - human
OT  - immunology
OT  - protein myristoylation
COIS- Conflict of interest The authors declare that they have no conflicts of interest 
      regarding the contents of this article.
EDAT- 2022/06/07 06:00
MHDA- 2022/07/27 06:00
PMCR- 2022/06/03
CRDT- 2022/06/06 19:23
PHST- 2022/04/05 00:00 [received]
PHST- 2022/05/31 00:00 [revised]
PHST- 2022/06/01 00:00 [accepted]
PHST- 2022/06/07 06:00 [pubmed]
PHST- 2022/07/27 06:00 [medline]
PHST- 2022/06/06 19:23 [entrez]
PHST- 2022/06/03 00:00 [pmc-release]
AID - S0021-9258(22)00541-5 [pii]
AID - 102100 [pii]
AID - 10.1016/j.jbc.2022.102100 [doi]
PST - ppublish
SO  - J Biol Chem. 2022 Jul;298(7):102100. doi: 10.1016/j.jbc.2022.102100. Epub 2022 
      Jun 3.