National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01 GM120322
米国
American Heart Association
19POST34380439/Jingxian Li/2019-2020
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01 GM134035-01
米国
引用
ジャーナル: Nat Commun / 年: 2020 タイトル: Alternative splicing controls teneurin-latrophilin interaction and synapse specificity by a shape-shifting mechanism. 著者: Jingxian Li / Yuan Xie / Shaleeka Cornelius / Xian Jiang / Richard Sando / Szymon P Kordon / Man Pan / Katherine Leon / Thomas C Südhof / Minglei Zhao / Demet Araç / 要旨: The trans-synaptic interaction of the cell-adhesion molecules teneurins (TENs) with latrophilins (LPHNs/ADGRLs) promotes excitatory synapse formation when LPHNs simultaneously interact with FLRTs. ...The trans-synaptic interaction of the cell-adhesion molecules teneurins (TENs) with latrophilins (LPHNs/ADGRLs) promotes excitatory synapse formation when LPHNs simultaneously interact with FLRTs. Insertion of a short alternatively-spliced region within TENs abolishes the TEN-LPHN interaction and switches TEN function to specify inhibitory synapses. How alternative-splicing regulates TEN-LPHN interaction remains unclear. Here, we report the 2.9 Å resolution cryo-EM structure of the TEN2-LPHN3 complex, and describe the trimeric TEN2-LPHN3-FLRT3 complex. The structure reveals that the N-terminal lectin domain of LPHN3 binds to the TEN2 barrel at a site far away from the alternatively spliced region. Alternative-splicing regulates the TEN2-LPHN3 interaction by hindering access to the LPHN-binding surface rather than altering it. Strikingly, mutagenesis of the LPHN-binding surface of TEN2 abolishes the LPHN3 interaction and impairs excitatory but not inhibitory synapse formation. These results suggest that a multi-level coincident binding mechanism mediated by a cryptic adhesion complex between TENs and LPHNs regulates synapse specificity.
全体 : Binary complex of human Teneurin-2 with human Latrophilin-3 extra...
全体
名称: Binary complex of human Teneurin-2 with human Latrophilin-3 extracellular domain
要素
複合体: Binary complex of human Teneurin-2 with human Latrophilin-3 extracellular domain
タンパク質・ペプチド: Teneurin-2
タンパク質・ペプチド: Adhesion G protein-coupled receptor L3
リガンド: 2-acetamido-2-deoxy-beta-D-glucopyranose
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超分子 #1: Binary complex of human Teneurin-2 with human Latrophilin-3 extra...
超分子
名称: Binary complex of human Teneurin-2 with human Latrophilin-3 extracellular domain タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#2 詳細: The binary complex includes human Teneurin2 (TENM2) (Teneurin without alternative splice sequence NKEFKHS) and human Latrophilin3 (LPHN3/ADGRL3) with an alternative splice sequence KVEQK ...詳細: The binary complex includes human Teneurin2 (TENM2) (Teneurin without alternative splice sequence NKEFKHS) and human Latrophilin3 (LPHN3/ADGRL3) with an alternative splice sequence KVEQK between lectin domain and olfactomedin domain.