Structural and functional analysis of the costimulatory receptor programmed death-1

被引：404

作者：

Zhang, XW

Schwartz, JCD

Guo, XL

Bhatia, S

Cao, EH

Chen, LP

Zhang, ZY

Edidin, MA

Nathenson, SG ^{[1
]}

Almo, SC

机构：

[1] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA

[2] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA

[3] Albert Einstein Coll Med, Dept Pharmacol, Bronx, NY 10461 USA

[4] Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10461 USA

[5] Albert Einstein Coll Med, Dept Physiol & Biophys, Bronx, NY 10461 USA

[6] Albert Einstein Coll Med, Ctr Synchrotron Biosci, Bronx, NY 10461 USA

[7] Mayo Clin & Mayo Fdn, Dept Immunol, Rochester, MN 55905 USA

[8] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA

来源：

IMMUNITY | 2004年 / 20卷 / 03期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/S1074-7613(04)00051-2

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

PD-1, a member of the CD28/CTLA-4/ICOS costimulatory receptor family, delivers negative signals that have profound effects on T and B cell immunity. The 2.0 A crystal structure of the extracellular domain of murine PD-1 reveals an Ig V-type topology with overall similarity to the CTLA-4 monomer; however, there are notable differences in regions relevant to function. Our structural and biophysical data show that PD-1 is monomeric both in solution as well as on cell surface, in contrast to CTLA-4 and other family members that are all disulfide-linked homodimers. Furthermore, our structure-based mutagenesis studies identify the ligand binding surface of PD-1, which displays significant differences compared to those present in the other members of the family.

引用

页码：337 / 347

页数：11

共 38 条

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