4mt7

Crystal structure of collybistin ICrystal structure of collybistin I

Structural highlights

4mt7 is a 1 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ARHG9_RAT Acts as guanine nucleotide exchange factor (GEF) for CDC42. Promotes formation of GPHN clusters.^[1] ^[2] ^[3]

Publication Abstract from PubMed

The formation of neuronal synapses and the dynamic regulation of their efficacy depend on the assembly of the postsynaptic neurotransmitter receptor apparatus. Receptor recruitment to inhibitory GABAergic and glycinergic synapses is controlled by the scaffold protein gephyrin and the adaptor protein collybistin. We derived new insights into the structure of collybistin and used these to design biochemical, cell biological, and genetic analyses of collybistin function. Our data define a collybistin-based protein interaction network that controls the gephyrin content of inhibitory postsynapses. Within this network, collybistin can adopt open/active and closed/inactive conformations to act as a switchable adaptor that links gephyrin to plasma membrane phosphoinositides. This function of collybistin is regulated by binding of the adhesion protein neuroligin-2, which stabilizes the open/active conformation of collybistin at the postsynaptic plasma membrane by competing with an intramolecular interaction in collybistin that favors the closed/inactive conformation. By linking trans-synaptic neuroligin-dependent adhesion and phosphoinositide signaling with gephyrin recruitment, the collybistin-based regulatory switch mechanism represents an integrating regulatory node in the formation and function of inhibitory postsynapses.

A conformational switch in collybistin determines the differentiation of inhibitory postsynapses.,Soykan T, Schneeberger D, Tria G, Buechner C, Bader N, Svergun D, Tessmer I, Poulopoulos A, Papadopoulos T, Varoqueaux F, Schindelin H, Brose N EMBO J. 2014 Jul 30. pii: e201488143. PMID:25082542^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kins S, Betz H, Kirsch J. Collybistin, a newly identified brain-specific GEF, induces submembrane clustering of gephyrin. Nat Neurosci. 2000 Jan;3(1):22-9. PMID:10607391 doi:http://dx.doi.org/10.1038/71096
↑ Grosskreutz Y, Hermann A, Kins S, Fuhrmann JC, Betz H, Kneussel M. Identification of a gephyrin-binding motif in the GDP/GTP exchange factor collybistin. Biol Chem. 2001 Oct;382(10):1455-62. PMID:11727829 doi:http://dx.doi.org/10.1515/BC.2001.179
↑ Harvey K, Duguid IC, Alldred MJ, Beatty SE, Ward H, Keep NH, Lingenfelter SE, Pearce BR, Lundgren J, Owen MJ, Smart TG, Luscher B, Rees MI, Harvey RJ. The GDP-GTP exchange factor collybistin: an essential determinant of neuronal gephyrin clustering. J Neurosci. 2004 Jun 23;24(25):5816-26. PMID:15215304 doi:10.1523/JNEUROSCI.1184-04.2004
↑ Soykan T, Schneeberger D, Tria G, Buechner C, Bader N, Svergun D, Tessmer I, Poulopoulos A, Papadopoulos T, Varoqueaux F, Schindelin H, Brose N. A conformational switch in collybistin determines the differentiation of inhibitory postsynapses. EMBO J. 2014 Jul 30. pii: e201488143. PMID:25082542 doi:http://dx.doi.org/10.15252/embj.201488143

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OCA

[1] Kins S, Betz H, Kirsch J. Collybistin, a newly identified brain-specific GEF, induces submembrane clustering of gephyrin. Nat Neurosci. 2000 Jan;3(1):22-9. PMID:10607391 doi:http://dx.doi.org/10.1038/71096

[2] Grosskreutz Y, Hermann A, Kins S, Fuhrmann JC, Betz H, Kneussel M. Identification of a gephyrin-binding motif in the GDP/GTP exchange factor collybistin. Biol Chem. 2001 Oct;382(10):1455-62. PMID:11727829 doi:http://dx.doi.org/10.1515/BC.2001.179

[3] Harvey K, Duguid IC, Alldred MJ, Beatty SE, Ward H, Keep NH, Lingenfelter SE, Pearce BR, Lundgren J, Owen MJ, Smart TG, Luscher B, Rees MI, Harvey RJ. The GDP-GTP exchange factor collybistin: an essential determinant of neuronal gephyrin clustering. J Neurosci. 2004 Jun 23;24(25):5816-26. PMID:15215304 doi:10.1523/JNEUROSCI.1184-04.2004

[4] Soykan T, Schneeberger D, Tria G, Buechner C, Bader N, Svergun D, Tessmer I, Poulopoulos A, Papadopoulos T, Varoqueaux F, Schindelin H, Brose N. A conformational switch in collybistin determines the differentiation of inhibitory postsynapses. EMBO J. 2014 Jul 30. pii: e201488143. PMID:25082542 doi:http://dx.doi.org/10.15252/embj.201488143

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