| Structural highlights
6vhh is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , |
| Gene: | TENM2, KIAA1127, ODZ2, TNM2 (HUMAN), ADGRL3, KIAA0768, LEC3, LPHN3 (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
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 PubMed
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 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 Also
References
- ↑ Silva JP, Lelianova VG, Ermolyuk YS, Vysokov N, Hitchen PG, Berninghausen O, Rahman MA, Zangrandi A, Fidalgo S, Tonevitsky AG, Dell A, Volynski KE, Ushkaryov YA. Latrophilin 1 and its endogenous ligand Lasso/teneurin-2 form a high-affinity transsynaptic receptor pair with signaling capabilities. Proc Natl Acad Sci U S A. 2011 Jul 19;108(29):12113-8. doi:, 10.1073/pnas.1019434108. Epub 2011 Jul 1. PMID:21724987 doi:http://dx.doi.org/10.1073/pnas.1019434108
- ↑ Silva JP, Lelianova VG, Ermolyuk YS, Vysokov N, Hitchen PG, Berninghausen O, Rahman MA, Zangrandi A, Fidalgo S, Tonevitsky AG, Dell A, Volynski KE, Ushkaryov YA. Latrophilin 1 and its endogenous ligand Lasso/teneurin-2 form a high-affinity transsynaptic receptor pair with signaling capabilities. Proc Natl Acad Sci U S A. 2011 Jul 19;108(29):12113-8. doi:, 10.1073/pnas.1019434108. Epub 2011 Jul 1. PMID:21724987 doi:http://dx.doi.org/10.1073/pnas.1019434108
- ↑ Lu YC, Nazarko OV, Sando R 3rd, Salzman GS, Sudhof TC, Arac D. Structural Basis of Latrophilin-FLRT-UNC5 Interaction in Cell Adhesion. Structure. 2015 Jul 28. pii: S0969-2126(15)00277-4. doi:, 10.1016/j.str.2015.06.024. PMID:26235030 doi:http://dx.doi.org/10.1016/j.str.2015.06.024
- ↑ Li J, Xie Y, Cornelius S, Jiang X, Sando R, Kordon SP, Pan M, Leon K, Sudhof TC, Zhao M, Arac D. Alternative splicing controls teneurin-latrophilin interaction and synapse specificity by a shape-shifting mechanism. Nat Commun. 2020 May 1;11(1):2140. doi: 10.1038/s41467-020-16029-7. PMID:32358586 doi:http://dx.doi.org/10.1038/s41467-020-16029-7
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