Structural insights into modulation and selectivity of transsynaptic neurexin-LRRTM interaction.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30262834.
- Also identified by DOI 10.1038/s41467-018-06333-8 and PMC identifier 6160412.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Leucine-rich repeat transmembrane neuronal proteins (LRRTMs) function as postsynaptic organizers that induce excitatory synapses. Neurexins (Nrxns) and heparan sulfate proteoglycans have been identified as presynaptic ligands for LRRTMs. Specifically, LRRTM1 and LRRTM2 bind to the Nrxn splice variant lacking an insert at the splice site 4 (S4). Here, we report the crystal structure of the Nrxn1β-LRRTM2 complex at 3.4 Å resolution. The Nrxn1β-LRRTM2 interface involves Ca<sup>2+</sup>-mediated interactions and overlaps with the Nrxn-neuroligin interface. Together with structure-based mutational analyses at the molecular and cellular levels, the present structural analysis unveils the mechanism of selective binding between Nrxn and LRRTM1/2 and its modulation by the S4 insertion of Nrxn.
Medical subject headings
- Cell Adhesion Molecules, Neuronal
- Membrane Proteins
- Nerve Tissue Proteins
- Neural Cell Adhesion Molecules
- Synapses