The Structure of Neurexin 1[alpha] Reveals Features Promoting a Role as Synaptic Organizer

Journal Article · Thu Oct 02 04:00:00 EDT 2014 · Structure

DOI:https://doi.org/10.1016/j.str.2011.03.012· OSTI ID:1031378

Chen, Fang; Venugopal, Vandavasi; Murray, Beverly; Rudenko, Gabby ^[1]

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1. Michigan

{alpha}-Neurexins are essential synaptic adhesion molecules implicated in autism spectrum disorder and schizophrenia. The {alpha}-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 {alpha}-neurexins might function as synaptic organizers, we solved the structure of the neurexin 1{alpha} extracellular domain (n1{alpha}) to 2.65 {angstrom}. 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 {angstrom} structure of n1{alpha} carrying splice insert SS3 in LNS4 reveals that SS3 protrudes as a loop and does not alter the rigid arrangement of repeat II. The global architecture imposed by conserved structural features enables {alpha}-neurexins to recruit and organize proteins in distinct and variable ways, influenced by splicing, thereby promoting synaptic function.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: OTHER
• OSTI ID: 1031378
• Journal Information: Structure, Journal Name: Structure Journal Issue: (6) ; 06, 2011 Vol. 19
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
ADHESION
ARCHITECTURE
FLEXIBILITY
PROTEINS
SPLICING