6vhh | pdb_00006vhh
Human Teneurin-2 and human Latrophilin-3 binary complex
Structural highlights
Function[TEN2_HUMAN] Involved in neural development, regulating the establishment of proper connectivity within the nervous system. Promotes the formation of filopodia and enlarged growth cone in neuronal cells. Induces homophilic cell-cell adhesion (By similarity). May function as a cellular signal transducer.[1] Acts as a ligand of the ADGRL1 receptor. Mediates axon guidance and heterophilic cell-cell adhesion.[2] Induces gene transcription inhibition. [AGRL3_HUMAN] Plays a role in cell-cell adhesion and neuron guidance via its interactions with FLRT2 and FLRT3 that are expressed at the surface of adjacent cells (PubMed:26235030). Plays a role in the development of glutamatergic synapses in the cortex. Important in determining the connectivity rates between the principal neurons in the cortex.[UniProtKB:Q80TS3][3] Publication Abstract from PubMedThe 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 A 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. Alternative splicing controls teneurin-latrophilin interaction and synapse specificity by a shape-shifting mechanism.,Li J, Xie Y, Cornelius S, Jiang X, Sando R, Kordon SP, Pan M, Leon K, Sudhof TC, Zhao M, Arac D Nat Commun. 2020 May 1;11(1):2140. doi: 10.1038/s41467-020-16029-7. PMID:32358586[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
