A dimeric structure of PD-L1: functional units or evolutionary relics?

被引:67
作者
Chen, Yong [1 ,2 ,4 ]
Liu, Peipei [1 ,2 ]
Gao, Feng [3 ]
Cheng, Hao [1 ,2 ]
Qi, Jianxun [1 ]
Gao, George F. [1 ,2 ,4 ,5 ]
机构
[1] Chinese Acad Sci CASPMI, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing 100101, Peoples R China
[2] Chinese Acad Sci, Grad Univ, Coll Life Sci, Beijing 100049, Peoples R China
[3] Chinese Acad Sci, Inst Biophys, Beijing 100101, Peoples R China
[4] Chinese Acad Sci, Inst Microbiol, China Japan Joint Lab Mol Immunol & Mol Microbiol, Beijing 100101, Peoples R China
[5] Chinese Acad Sci, Beijing Inst Life Sci, Beijing 100101, Peoples R China
关键词
PD-L1; crystal structure; dimer; costimulatory molecules; B7; family; RECEPTOR-BINDING DOMAIN; CRYSTAL-STRUCTURE; IMMUNOLOGICAL SYNAPSE; PD-1/PD-L1; BLOCKADE; COMPLEX; EXPRESSION; FAMILY; CRYSTALLIZATION; PROTEIN; MEMBER;
D O I
10.1007/s13238-010-0022-1
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
PD-L1 is a member of the B7 protein family, most of whose members so far were identified as dimers in a solution and crystalline state, either complexed or uncomplexed with their ligand(s). The binding of PD-L1 with its receptor PD-1 (CD279) delivers an inhibitory signal regulating the T cell function. Simultaneously with the Garboczi group, we successfully solved another structure of human PD-L1 (hPD-L1). Our protein crystallized in the space group of C222(1) with two hPD-L1 molecules per asymmetric unit. After comparison of reported B7 structures, we have found some intrinsic factors involved in the interaction of these two molecules. Based on these results, we tend to believe this uncomplexed hPD-L1 structure demonstrated its potential dimeric state in solution, althougt it could just be an evolutionary relic, too weak to be detected under present technology, or still a functional unit deserved our attentions.
引用
收藏
页码:153 / 160
页数:8
相关论文
共 35 条
[1]   THE CCP4 SUITE - PROGRAMS FOR PROTEIN CRYSTALLOGRAPHY [J].
BAILEY, S .
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1994, 50 :760-763
[2]   The immunological synapse and CD28-CD80 interactions [J].
Bromley, SK ;
Iaboni, A ;
Davis, SJ ;
Whitty, A ;
Green, JM ;
Shaw, AS ;
Weiss, A ;
Dustin, ML .
NATURE IMMUNOLOGY, 2001, 2 (12) :1159-1166
[3]   Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity [J].
Chen, LP .
NATURE REVIEWS IMMUNOLOGY, 2004, 4 (05) :336-347
[4]   Stability engineering, biophysical, and biological characterization of the myeloid activating receptor immunoglobulin-like transcript 1 (ILT1/LIR-7/LILRA2) [J].
Chen, Yong ;
Chu, Fuliang ;
Gao, Feng ;
Zhou, Bin ;
Gao, George F. .
PROTEIN EXPRESSION AND PURIFICATION, 2007, 56 (02) :253-260
[5]   Crystal Structure of Myeloid Cell Activating Receptor Leukocyte Ig-like Receptor A2 (LILRA2/ILT1/LIR-7) Domain Swapped Dimer: Molecular Basis for Its Non-binding to MHC Complexes [J].
Chen, Yong ;
Gao, Feng ;
Chu, Fuliang ;
Peng, Hao ;
Zong, Lili ;
Liu, Yiwei ;
Tien, Po ;
Gao, George F. .
JOURNAL OF MOLECULAR BIOLOGY, 2009, 386 (03) :841-853
[6]   Cytotoxic T lymphocyte antigen-4 accumulation in the immunological synapse is regulated by TCR signal strength [J].
Egen, JG ;
Allison, JP .
IMMUNITY, 2002, 16 (01) :23-35
[7]   Insulin-induced remission in new-onset NOD mice is maintained by the PD-1-PD-L1 pathway [J].
Fife, Brian T. ;
Guleria, Indira ;
Bupp, Melanie Gubbels ;
Eagar, Todd N. ;
Tang, Qizhi ;
Bour-Jordan, Helene ;
Yagita, Hideo ;
Azuma, Miyuki ;
Sayegh, Mohamed H. ;
Bluestone, Jeffrey A. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2006, 203 (12) :2737-2747
[8]   PD-1/PD-L1 blockade can improve the HBV-specific T cell function in chronic hbv infection [J].
Fisicaro, P. ;
Boni, C. ;
Valdatta, C. ;
Bertoletti, A. ;
Schivazappa, S. ;
Giuberti, T. ;
Cavalli, A. ;
Missale, G. ;
Ferrari, C. .
JOURNAL OF HEPATOLOGY, 2007, 46 :S56-S56
[9]   Crystal structure of the human natural killer (NK) cell activating receptor NKp46 reveals structural relationship to other leukocyte receptor complex immunoreceptors [J].
Foster, CE ;
Colonna, M ;
Sun, PD .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (46) :46081-46086
[10]   Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation [J].
Freeman, GJ ;
Long, AJ ;
Iwai, Y ;
Bourque, K ;
Chernova, T ;
Nishimura, H ;
Fitz, LJ ;
Malenkovich, N ;
Okazaki, T ;
Byrne, MC ;
Horton, HF ;
Fouser, L ;
Carter, L ;
Ling, V ;
Bowman, MR ;
Carreno, BM ;
Collins, M ;
Wood, CR ;
Honjo, T .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (07) :1027-1034