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Title: The Crystal Structure of Cdc42 in Complex with Collybisin II, a Gephyrin-Interacting Guanine Nucleotide Exchange Factor

Abstract

The synaptic localization of ion channel receptors is essential for efficient synaptic transmission and the precise regulation of diverse neuronal functions. In the central nervous system, ion channel receptors reside in the postsynaptic membrane where they are juxtaposed to presynaptic terminals. For proper function, these ion channels have to be anchored to the cytoskeleton, and in the case of the inhibitory glycine and {gamma}-amino-butyric acid type A (GABA{sub A}) receptors this interaction is mediated by a gephyrin centered scaffold. Highlighting its central role in this receptor anchoring scaffold, gephyrin interacts with a number of proteins, including the neurospecific guanine nucleotide exchange factor collybistin. Collybistin belongs to the Dbl family of guanine nucleotide exchange factors, occurs in multiple splice variants, and is specific for Cdc42, a small GTPase belonging to the Rho family. The 2.3 Angstroms resolution crystal structure of the Cdc42--collybistin II complex reveals a novel conformation of the switch I region of Cdc42. It also provides the first direct observation of structural changes in the relative orientation of the Dbl-homology domain and the pleckstrin-homology domain in the same Dbl family protein. Biochemical data indicate that gephyrin negatively regulates collybistin activity.

Authors:
; ; ; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
914320
Report Number(s):
BNL-78888-2007-JA
Journal ID: ISSN 0022-2836; JMOBAK; TRN: US200809%%175
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Journal Name:
J. Mol. Biol.
Additional Journal Information:
Journal Volume: 359; Journal Issue: 1; Journal ID: ISSN 0022-2836
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; CENTRAL NERVOUS SYSTEM; CRYSTAL STRUCTURE; GLYCINE; GUANINE; MEMBRANES; NUCLEOTIDES; ORIENTATION; PROTEINS; REGULATIONS; RESOLUTION; national synchrotron light source

Citation Formats

Xiang, S, Kim, E, Connelly, J, Nassar, N, Kirsch, J, WinkingSchwartz, G, and Schindelin, H. The Crystal Structure of Cdc42 in Complex with Collybisin II, a Gephyrin-Interacting Guanine Nucleotide Exchange Factor. United States: N. p., 2006. Web. doi:10.1016/j.jmb.2006.03.019.
Xiang, S, Kim, E, Connelly, J, Nassar, N, Kirsch, J, WinkingSchwartz, G, & Schindelin, H. The Crystal Structure of Cdc42 in Complex with Collybisin II, a Gephyrin-Interacting Guanine Nucleotide Exchange Factor. United States. https://doi.org/10.1016/j.jmb.2006.03.019
Xiang, S, Kim, E, Connelly, J, Nassar, N, Kirsch, J, WinkingSchwartz, G, and Schindelin, H. 2006. "The Crystal Structure of Cdc42 in Complex with Collybisin II, a Gephyrin-Interacting Guanine Nucleotide Exchange Factor". United States. https://doi.org/10.1016/j.jmb.2006.03.019.
@article{osti_914320,
title = {The Crystal Structure of Cdc42 in Complex with Collybisin II, a Gephyrin-Interacting Guanine Nucleotide Exchange Factor},
author = {Xiang, S and Kim, E and Connelly, J and Nassar, N and Kirsch, J and WinkingSchwartz, G and Schindelin, H},
abstractNote = {The synaptic localization of ion channel receptors is essential for efficient synaptic transmission and the precise regulation of diverse neuronal functions. In the central nervous system, ion channel receptors reside in the postsynaptic membrane where they are juxtaposed to presynaptic terminals. For proper function, these ion channels have to be anchored to the cytoskeleton, and in the case of the inhibitory glycine and {gamma}-amino-butyric acid type A (GABA{sub A}) receptors this interaction is mediated by a gephyrin centered scaffold. Highlighting its central role in this receptor anchoring scaffold, gephyrin interacts with a number of proteins, including the neurospecific guanine nucleotide exchange factor collybistin. Collybistin belongs to the Dbl family of guanine nucleotide exchange factors, occurs in multiple splice variants, and is specific for Cdc42, a small GTPase belonging to the Rho family. The 2.3 Angstroms resolution crystal structure of the Cdc42--collybistin II complex reveals a novel conformation of the switch I region of Cdc42. It also provides the first direct observation of structural changes in the relative orientation of the Dbl-homology domain and the pleckstrin-homology domain in the same Dbl family protein. Biochemical data indicate that gephyrin negatively regulates collybistin activity.},
doi = {10.1016/j.jmb.2006.03.019},
url = {https://www.osti.gov/biblio/914320}, journal = {J. Mol. Biol.},
issn = {0022-2836},
number = 1,
volume = 359,
place = {United States},
year = {Sun Jan 01 00:00:00 EST 2006},
month = {Sun Jan 01 00:00:00 EST 2006}
}