PMID- 31273318
OWN - NLM
STAT- MEDLINE
DCOM- 20211006
LR  - 20211006
IS  - 2042-0226 (Electronic)
IS  - 1672-7681 (Print)
IS  - 1672-7681 (Linking)
VI  - 17
IP  - 9
DP  - 2020 Sep
TI  - Structures of the four Ig-like domain LILRB2 and the four-domain LILRB1 and 
      HLA-G1 complex.
PG  - 966-975
LID - 10.1038/s41423-019-0258-5 [doi]
AB  - Leukocyte immunoglobulin (Ig)-like receptors (LILRs), also known as CD85 and 
      immunoglobulin-like transcripts (ILTs), play pivotal roles in regulating immune 
      responses. These receptors define an immune checkpoint that immune therapy can 
      target. Through cis or trans interactions with human leukocyte antigen (HLA)-G, 
      the two most abundantly expressed inhibitory LILRs, LILRB1, and LILRB2 (LILRB1/2, 
      also known as CD85j/d and ILT2/4), are involved in immunotolerance in pregnancy 
      and transplantation, autoimmune diseases, and immune evasion by tumors. Although 
      the discrete domains of LILRB1/2 are clear, the assembly mode of the four 
      extracellular Ig-like domains (D1, D2, D3, and D4) remains unknown. Previous data 
      indicate that D1D2 is responsible for binding to HLA class I (HLA-I), but the 
      roles of D3D4 are still unclear. Here, we determined the crystal structure of the 
      four Ig-like domain LILRB2 and four-domain LILRB1 in complex with HLA-G1. The 
      angles between adjacent domains and the staggered assembly of the four domains 
      suggest limited flexibility and limited plasticity of the receptors during ligand 
      binding. The complex structure of four-domain LILRB1 and HLA-G1 supports the 
      model that D1D2 is responsible for HLA-I binding, while D3D4 acts as a scaffold. 
      Accordingly, cis and trans binding models for HLA-I binding to LILRB1/2 are 
      proposed. The geometries of LILRB1/2 in complex with dimeric and monomeric HLA-G1 
      suggest the accessibility of the dimeric receptor, which in turn, transduces more 
      inhibitory signals. The assembly of LILRB1/2 and its binding to HLA-G1 could aid 
      in the design of immune regulators and benefit immune interference.
FAU - Wang, Qihui
AU  - Wang Q
AUID- ORCID: 0000-0003-3768-0401
AD  - CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, 
      Institute of Microbiology, Chinese Academy of Sciences, 100101, Beijing, China. 
      wangqihui@im.ac.cn.
AD  - Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, 
      University of Texas Health Science Center at Houston, 77030, Houston, TX, USA. 
      wangqihui@im.ac.cn.
FAU - Song, Hao
AU  - Song H
AD  - Research Network of Immunity and Health (RNIH), Beijing Institutes of Life 
      Science, Chinese Academy of Sciences, Beijing, 100101, China.
FAU - Cheng, Hao
AU  - Cheng H
AD  - Research Network of Immunity and Health (RNIH), Beijing Institutes of Life 
      Science, Chinese Academy of Sciences, Beijing, 100101, China.
FAU - Qi, Jianxun
AU  - Qi J
AD  - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of 
      Microbiology, Chinese Academy of Sciences, 100101, Beijing, China.
FAU - Nam, Gol
AU  - Nam G
AD  - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of 
      Microbiology, Chinese Academy of Sciences, 100101, Beijing, China.
FAU - Tan, Shuguang
AU  - Tan S
AD  - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of 
      Microbiology, Chinese Academy of Sciences, 100101, Beijing, China.
FAU - Wang, Junzhi
AU  - Wang J
AD  - Key Laboratory of the Ministry of Health for Research on Quality and 
      Standardization of Biotech Products, National Institutes for Food and Drug 
      Control, 100050, Beijing, China.
FAU - Fang, Min
AU  - Fang M
AUID- ORCID: 0000-0002-5278-1430
AD  - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of 
      Microbiology, Chinese Academy of Sciences, 100101, Beijing, China.
FAU - Shi, Yi
AU  - Shi Y
AUID- ORCID: 0000-0002-3053-2687
AD  - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of 
      Microbiology, Chinese Academy of Sciences, 100101, Beijing, China.
AD  - Savaid Medical School, University of Chinese Academy of Sciences, 101408, 
      Beijing, China.
FAU - Tian, Zhigang
AU  - Tian Z
AD  - Institute of Immunology and CAS Key Laboratory of Innate Immunity and Chronic 
      Disease, School of Life Sciences and Medical Center, University of Science and 
      Technology of China, 230027, Hefei, China.
FAU - Cao, Xuetao
AU  - Cao X
AD  - National Key Laboratory of Medical Immunology & Institute of Immunology, Second 
      Military Medical University, 200433, Shanghai, China.
AD  - Department of Immunology & Center for Immunotherapy, Institute of Basic Medical 
      Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, 
      100005, Beijing, China.
FAU - An, Zhiqiang
AU  - An Z
AD  - Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, 
      University of Texas Health Science Center at Houston, 77030, Houston, TX, USA.
FAU - Yan, Jinghua
AU  - Yan J
AUID- ORCID: 0000-0003-0502-3829
AD  - CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, 
      Institute of Microbiology, Chinese Academy of Sciences, 100101, Beijing, China.
AD  - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of 
      Microbiology, Chinese Academy of Sciences, 100101, Beijing, China.
AD  - College of Life Sciences, University of Chinese Academy of Sciences, 100049, 
      Beijing, China.
FAU - Gao, George F
AU  - Gao GF
AUID- ORCID: 0000-0002-3869-615X
AD  - Research Network of Immunity and Health (RNIH), Beijing Institutes of Life 
      Science, Chinese Academy of Sciences, Beijing, 100101, China. gaof@im.ac.cn.
AD  - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of 
      Microbiology, Chinese Academy of Sciences, 100101, Beijing, China. gaof@im.ac.cn.
AD  - Savaid Medical School, University of Chinese Academy of Sciences, 101408, 
      Beijing, China. gaof@im.ac.cn.
AD  - Collaborative Innovation Center for diagnosis and treatment of infectious 
      diseases, Zhejiang University, 310003, Hangzhou, China. gaof@im.ac.cn.
AD  - National Institute for Viral Disease Control and Prevention, Chinese Center for 
      Disease Control and Prevention (China CDC), 102206, Beijing, China. 
      gaof@im.ac.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190704
PL  - China
TA  - Cell Mol Immunol
JT  - Cellular & molecular immunology
JID - 101242872
RN  - 0 (HLA-G Antigens)
RN  - 0 (Immunoglobulins)
RN  - 0 (Leukocyte Immunoglobulin-like Receptor B1)
RN  - 0 (Ligands)
SB  - IM
MH  - Alleles
MH  - HLA-G Antigens/*chemistry/*metabolism
MH  - Immunoglobulins/*chemistry
MH  - Leukocyte Immunoglobulin-like Receptor B1/*chemistry/*metabolism
MH  - Ligands
MH  - Models, Molecular
MH  - Protein Binding
MH  - Protein Domains
MH  - Structural Homology, Protein
PMC - PMC7609294
OTO - NOTNLM
OT  - HLA-G
OT  - LILRB1
OT  - LILRB2
OT  - checkpoint
OT  - structural studies
COIS- The authors declare no competing interests.
EDAT- 2019/07/06 06:00
MHDA- 2021/10/07 06:00
PMCR- 2021/09/01
CRDT- 2019/07/06 06:00
PHST- 2018/12/14 00:00 [received]
PHST- 2019/06/14 00:00 [accepted]
PHST- 2019/07/06 06:00 [pubmed]
PHST- 2021/10/07 06:00 [medline]
PHST- 2019/07/06 06:00 [entrez]
PHST- 2021/09/01 00:00 [pmc-release]
AID - 10.1038/s41423-019-0258-5 [pii]
AID - 258 [pii]
AID - 10.1038/s41423-019-0258-5 [doi]
PST - ppublish
SO  - Cell Mol Immunol. 2020 Sep;17(9):966-975. doi: 10.1038/s41423-019-0258-5. Epub 
      2019 Jul 4.