TY - JOUR
T1 - The structure of neurexin 1α reveals features promoting a role as synaptic organizer
AU - Chen, Fang
AU - Venugopal, Vandavasi
AU - Murray, Beverly
AU - Rudenko, Gabby
N1 - Funding Information:
This work was funded by NIMH RO1 MH077303 and would not have been possible without funds from the American Recovery and Reinvestment Act 3R01MH077303-04S1. We thank Dr. T. Südhof for the n1α cDNA, Dr. D. Borek for advice on data processing, Dr. S. Anderson for excellent beamline support, I. Wu for initial crystallization experiments, and Dr. C. Brown for reagents. Diffraction data were collected at LS-CAT (beam-line 21-ID-D) at the Advanced Photon Source, Argonne National Laboratories. F.C. performed molecular biology, protein purification, and crystallization. V.V. performed crystallization, and structure determination of n1α+SS#3. B.M. performed molecular biology. G.R. conceived the research plan, performed protein purification, crystallization, structure determination of n1α, and wrote the manuscript.
PY - 2011/6/8
Y1 - 2011/6/8
N2 - α-Neurexins are essential synaptic adhesion molecules implicated in autism spectrum disorder and schizophrenia. The α-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 α-neurexins might function as synaptic organizers, we solved the structure of the neurexin 1α extracellular domain (n1α) to 2.65 . 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 structure of n1α 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 α-neurexins to recruit and organize proteins in distinct and variable ways, influenced by splicing, thereby promoting synaptic function.
AB - α-Neurexins are essential synaptic adhesion molecules implicated in autism spectrum disorder and schizophrenia. The α-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 α-neurexins might function as synaptic organizers, we solved the structure of the neurexin 1α extracellular domain (n1α) to 2.65 . 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 structure of n1α 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 α-neurexins to recruit and organize proteins in distinct and variable ways, influenced by splicing, thereby promoting synaptic function.
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U2 - 10.1016/j.str.2011.03.012
DO - 10.1016/j.str.2011.03.012
M3 - Article
C2 - 21620716
AN - SCOPUS:79958159261
SN - 0969-2126
VL - 19
SP - 779
EP - 789
JO - Structure
JF - Structure
IS - 6
ER -