PMID- 37751693
OWN - NLM
STAT- MEDLINE
DCOM- 20230928
LR  - 20231005
IS  - 2667-2375 (Electronic)
IS  - 2667-2375 (Linking)
VI  - 3
IP  - 9
DP  - 2023 Sep 25
TI  - Hybrid structural modeling of alloantibody binding to human leukocyte antigen 
      with rapid and reproducible cross-linking mass spectrometry.
PG  - 100569
LID - S2667-2375(23)00213-8 [pii]
LID - 10.1016/j.crmeth.2023.100569 [doi]
LID - 100569
AB  - Alloantibody recognition of donor human leukocyte antigen (HLA) is associated 
      with poor clinical transplantation outcomes. However, the molecular and 
      structural basis for the alloantibody-HLA interaction is not well understood. 
      Here, we used a hybrid structural modeling approach on a previously studied 
      alloantibody-HLA interacting pair with inputs from ab initio, in silico, and 
      in vitro data. Highly reproducible cross-linking mass spectrometry data were 
      obtained with both discovery- and targeted mass spectrometry-based approaches 
      approaches. The cross-link information was then used together with predicted 
      antibody F(v) structure, predicted antibody paratope, and in silico-predicted 
      interacting surface to model the antibody-HLA interaction. This hybrid structural 
      modeling approach closely recapitulates the key interacting residues from a 
      previously solved crystal structure of an alloantibody-HLA-A *11:01 pair. These 
      results suggest that a predictive-based hybrid structural modeling approach 
      supplemented with cross-linking mass spectrometry data can provide functionally 
      relevant structural models to understand the structural basis of antibody-HLA 
      mismatch in transplantation.
CI  - Copyright (c) 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Ser, Zheng
AU  - Ser Z
AD  - Functional Proteomics Laboratory, SingMass National Laboratory, Institute of 
      Molecular and Cell Biology, Agency for Science, Technology and Research (A *STAR), 
      Singapore 138673, Singapore.
FAU - Gu, Yue
AU  - Gu Y
AD  - Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, 
      National University of Singapore, 5 Science Drive 2, Singapore 117545, Singapore; 
      Immunology Translational Research Programme, Yong Loo Lin School of Medicine, 
      National University of Singapore, 5 Science Drive 2, Singapore 117545, Singapore.
FAU - Yap, Jiawei
AU  - Yap J
AD  - Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, 
      National University of Singapore, 5 Science Drive 2, Singapore 117545, Singapore; 
      Immunology Translational Research Programme, Yong Loo Lin School of Medicine, 
      National University of Singapore, 5 Science Drive 2, Singapore 117545, Singapore.
FAU - Lim, Yan Ting
AU  - Lim YT
AD  - Functional Proteomics Laboratory, SingMass National Laboratory, Institute of 
      Molecular and Cell Biology, Agency for Science, Technology and Research (A *STAR), 
      Singapore 138673, Singapore.
FAU - Wang, Shi Mei
AU  - Wang SM
AD  - Functional Proteomics Laboratory, SingMass National Laboratory, Institute of 
      Molecular and Cell Biology, Agency for Science, Technology and Research (A *STAR), 
      Singapore 138673, Singapore.
FAU - Hamidinia, Maryam
AU  - Hamidinia M
AD  - Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, 
      National University of Singapore, 5 Science Drive 2, Singapore 117545, Singapore; 
      Immunology Translational Research Programme, Yong Loo Lin School of Medicine, 
      National University of Singapore, 5 Science Drive 2, Singapore 117545, Singapore.
FAU - Murali, Tanusya Murali
AU  - Murali TM
AD  - Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, 
      National University of Singapore, 5 Science Drive 2, Singapore 117545, Singapore; 
      Immunology Translational Research Programme, Yong Loo Lin School of Medicine, 
      National University of Singapore, 5 Science Drive 2, Singapore 117545, Singapore.
FAU - Kumar, Ragini
AU  - Kumar R
AD  - Functional Proteomics Laboratory, SingMass National Laboratory, Institute of 
      Molecular and Cell Biology, Agency for Science, Technology and Research (A *STAR), 
      Singapore 138673, Singapore.
FAU - Gascoigne, Nicholas Rj
AU  - Gascoigne NR
AD  - Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, 
      National University of Singapore, 5 Science Drive 2, Singapore 117545, Singapore; 
      Immunology Translational Research Programme, Yong Loo Lin School of Medicine, 
      National University of Singapore, 5 Science Drive 2, Singapore 117545, Singapore.
FAU - MacAry, Paul A
AU  - MacAry PA
AD  - Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, 
      National University of Singapore, 5 Science Drive 2, Singapore 117545, Singapore; 
      Immunology Translational Research Programme, Yong Loo Lin School of Medicine, 
      National University of Singapore, 5 Science Drive 2, Singapore 117545, Singapore.
FAU - Sobota, Radoslaw M
AU  - Sobota RM
AD  - Functional Proteomics Laboratory, SingMass National Laboratory, Institute of 
      Molecular and Cell Biology, Agency for Science, Technology and Research (A *STAR), 
      Singapore 138673, Singapore. Electronic address: rmsobota@imcb.a-star.edu.sg.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230830
PL  - United States
TA  - Cell Rep Methods
JT  - Cell reports methods
JID - 9918227360606676
RN  - 0 (Histocompatibility Antigens)
RN  - 0 (HLA Antigens)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Isoantibodies)
RN  - 0 (Immunoglobulin Variable Region)
SB  - IM
MH  - Humans
MH  - *Histocompatibility Antigens
MH  - *HLA Antigens
MH  - Histocompatibility Antigens Class II
MH  - Isoantibodies
MH  - Immunoglobulin Variable Region
MH  - Mass Spectrometry
PMC - PMC10545907
OTO - NOTNLM
OT  - CP: Immunology
OT  - HLA
OT  - antibody
OT  - cross-linking mass spectrometry
OT  - human leukocyte antigen
OT  - mass spectrometry
OT  - molecular docking
OT  - proteomics
OT  - structural biology
OT  - transplantation
COIS- Declaration of interests The authors declare no competing interests.
EDAT- 2023/09/27 00:42
MHDA- 2023/09/28 06:43
PMCR- 2023/08/30
CRDT- 2023/09/26 18:17
PHST- 2023/03/16 00:00 [received]
PHST- 2023/06/05 00:00 [revised]
PHST- 2023/08/07 00:00 [accepted]
PHST- 2023/09/28 06:43 [medline]
PHST- 2023/09/27 00:42 [pubmed]
PHST- 2023/09/26 18:17 [entrez]
PHST- 2023/08/30 00:00 [pmc-release]
AID - S2667-2375(23)00213-8 [pii]
AID - 100569 [pii]
AID - 10.1016/j.crmeth.2023.100569 [doi]
PST - ppublish
SO  - Cell Rep Methods. 2023 Sep 25;3(9):100569. doi: 10.1016/j.crmeth.2023.100569. 
      Epub 2023 Aug 30.