The structure of neurexin 1? reveals features promoting a role as synaptic organizer.

ABSTRACT: ?-neurexins are essential synaptic adhesion molecules implicated in autism spectrum disorder and schizophrenia. The ?-neurexin extracellular domain consists of six LNS domains interspersed by three EGF-like repeats and interacts with many different proteins in the synaptic cleft. To understand how ?-neurexins might function as synaptic organizers, we solved the structure of the neurexin 1? extracellular domain (n1?) to 2.65 Å. The L-shaped molecule can be divided into a flexible repeat I (LNS1-EGF-A-LNS2), a rigid horseshoe-shaped repeat II (LNS3-EGF-B-LNS4) with structural similarity to so-called reelin repeats, and an extended repeat III (LNS5-EGF-B-LNS6) with controlled flexibility. A 2.95 Å structure of n1? carrying splice insert SS#3 in LNS4 reveals that SS#3 protrudes as a loop and does not alter the rigid arrangement of repeat II. The global architecture imposed by conserved structural features enables ?-neurexins to recruit and organize proteins in distinct and variable ways, influenced by splicing, thereby promoting synaptic function.

SUBMITTER: Chen F 

PROVIDER: S-EPMC3134934 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature