Structural Basis for Teneurin Function in Circuit-Wiring: A Toxin Motif at the Synapse

被引：97

作者：

Li, Jingxian ^{[1
,2
]}

Shalev-Benami, Moran ^{[3
,4
]}

Sando, Richard ^{[3
,5
]}

Jiang, Xian ^{[3
,5
]}

Kibrom, Amanuel ^{[1
,2
]}

Wang, Jie ^{[3
,5
]}

Leon, Katherine ^{[1
,2
]}

Katanski, Christopher ^{[1
,2
]}

Nazarko, Olha ^{[1
,2
]}

Lu, Yue C. ^{[1
,2
]}

Sudhof, Thomas C. ^{[3
,5
]}

Skiniotis, Georgios ^{[3
,4
]}

Arac, Demet ^{[1
,2
]}

机构：

[1] Univ Chicago, Dept Biochem & Mol Biol, 920 E 58Th St, Chicago, IL 60637 USA

[2] Univ Chicago, Grossman Inst Neurosci Quantitat Biol & Human Beh, Chicago, IL 60637 USA

[3] Stanford Univ, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA

[4] Stanford Univ, Dept Struct Biol, Stanford, CA 94305 USA

[5] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA

来源：

CELL | 2018年 / 173卷 / 03期

关键词：

CORTICOTROPIN-RELEASING-FACTOR; TERMINAL ASSOCIATED PEPTIDE; PHYLOGENETIC ANALYSIS; FACTOR CRF; FAMILY; EXPRESSION; GENERATION; MUTATIONS; NEURESTIN; MECHANISM;

D O I：

10.1016/j.cell.2018.03.036

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Teneurins (TENs) are cell-surface adhesion proteins with critical roles in tissue development and axon guidance. Here, we report the 3.1-angstrom cryoelectron microscopy structure of the human TEN2 extracellular region (ECR), revealing a striking similarity to bacterial Tc-toxins. The ECR includes a large beta barrel that partially encapsulates a C-terminal domain, which emerges to the solvent through an opening in the mid-barrel region. An immunoglobulin (Ig)-like domain seals the bottom of the barrel while a beta propeller is attached in a perpendicular orientation. We further show that an alternatively spliced region within the beta propeller acts as a switch to regulate transcellular adhesion of TEN2 to latrophilin (LPHN), a transmembrane receptor known to mediate critical functions in the central nervous system. One splice variant activates trans-cellular signaling in a LPHN-dependent manner, whereas the other induces inhibitory postsynaptic differentiation. These results highlight the unusual structural organization of TENs giving rise to their multifarious functions.

引用

页码：735 / +

页数：29

共 63 条

[1] PHENIX: a comprehensive Python']Python-based system for macromolecular structure solution [J].