6cmx | pdb_00006cmx
Human Teneurin 2 extra-cellular region
Structural highlights
FunctionTEN2_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. Publication Abstract from PubMedTeneurins (TENs) are cell-surface adhesion proteins with critical roles in tissue development and axon guidance. Here, we report the 3.1-A 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 trans-cellular 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. Structural Basis for Teneurin Function in Circuit-Wiring: A Toxin Motif at the Synapse.,Li J, Shalev-Benami M, Sando R, Jiang X, Kibrom A, Wang J, Leon K, Katanski C, Nazarko O, Lu YC, Sudhof TC, Skiniotis G, Arac D Cell. 2018 Apr 19;173(3):735-748.e15. doi: 10.1016/j.cell.2018.03.036. PMID:29677516[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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