期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 111, 期 49, 页码 17576-17581出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1420936111
关键词
T-cell receptor; electron microscopy; small-angle X-ray scattering
资金
- Regina Casper Stanford Graduate Fellowship
- Gerald J. Lieberman Fellowship
- National Science Foundation
- National Health and Medical Research Council (NHMRC) [GNT1035636]
- NHMRC Australia
- NIH [R01 AI03867]
- Howard Hughes Medical Institute
- NHMRC
- Australian Research Council
alpha beta T-cell receptor (TCR) activation plays a crucial role for T-cell function. However, the TCR itself does not possess signaling domains. Instead, the TCR is noncovalently coupled to a conserved multisubunit signaling apparatus, the CD3 complex, that comprises the CD3 epsilon gamma, CD3 epsilon delta, and CD3 zeta zeta dimers. How antigen ligation by the TCR triggers CD3 activation and what structural role the CD3 extracellular domains (ECDs) play in the assembled TCR-CD3 complex remain unclear. Here, we use two complementary structural approaches to gain insight into the overall organization of the TCR-CD3 complex. Small-angle X-ray scattering of the soluble TCR-CD3 epsilon delta complex reveals the CD3 epsilon delta ECDs to sit underneath the TCR alpha-chain. The observed arrangement is consistent with EM images of the entire TCR-CD3 integral membrane complex, in which the CD3 epsilon delta and CD3 epsilon gamma subunits were situated underneath the TCR alpha-chain and TCR beta-chain, respectively. Interestingly, the TCR-CD3 transmembrane complex bound to peptide-MHC is a dimer in which two TCRs project outward from a central core composed of the CD3 ECDs and the TCR and CD3 transmembrane domains. This arrangement suggests a potential ligand-dependent dimerization mechanism for TCR signaling. Collectively, our data advance our understanding of the molecular organization of the TCR-CD3 complex, and provides a conceptual framework for the TCR activation mechanism.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据