6VHH

Human Teneurin-2 and human Latrophilin-3 binary complex

Summary for 6VHH

• Entry DOI: 10.2210/pdb6vhh/pdb
• EMDB information: 21205
• Descriptor: Teneurin-2, Adhesion G protein-coupled receptor L3, alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: adhesion gpcr, synapse, teneurin, lphn, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 314574.08

Authors

Xie, Y.,Li, J.,Arac, D.,Zhao, M. (deposition date: 2020-01-09, release date: 2020-06-03, Last modification date: 2024-10-23)

Primary citation

Li, J.,Xie, Y.,Cornelius, S.,Jiang, X.,Sando, R.,Kordon, S.P.,Pan, M.,Leon, K.,Sudhof, T.C.,Zhao, M.,Arac, D.
Alternative splicing controls teneurin-latrophilin interaction and synapse specificity by a shape-shifting mechanism.
Nat Commun, 11:2140-2140, 2020

PubMed Abstract: 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.

PubMed: 32358586
DOI: 10.1038/s41467-020-16029-7

Experimental method

ELECTRON MICROSCOPY (2.97 Å)