Gephyrin: Difference between revisions

Latest revision as of 12:56, 12 March 2023

Function

Gephyrin (Gep) is responsible for Mo cofactor biosynthesis and for postsynaptic clustering of glycine receptors and type A GABA receptors in the vertebrate CNS. Gep self-assembles to form scaffolds in the synapse^[1].

Relevance

Abnormal accumulation of Gep are highly correlated with the neuropathologic diagnosis of Alzheimer Disease^[2].

Structural highlights

interacts with ^[3].

Rat gephyrin E domain (cyan) complex with glycine receptor peptides (magenta and pink), acetate and Ca+2 ion (green) (PDB code 4u91)

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3D structures of gephyrin3D structures of gephyrin

Updated on 12-March-2023

2fu3, 5erq, 4pd0 - rGeph E domain 318-736 - rat
2fts, 4pd1, 1t3e, 4u91 - rGeph E domain + glycine receptor peptide
6hso - rGeph E domain + glycine receptor peptide + ADP<br / 4tk1, 4tk2, 4tk3, 4tk4, 4u90 - rGeph E domain + GABA receptor peptide
6hsn - rGeph E domain + GABA receptor peptide + ADP
5ers - rGeph E domain + AMP
5ert, 5err - rGeph E domain + ADP
5eru - rGeph E domain + ADP + Mo + MoO4
5erv - rGeph E domain + ADP + W + WO4
6fgc - rGeph E domain + artesunate + ADP
6fgd - rGeph E domain + artemether + ADP
1ihc, 1jlj - rGeph N terminal
1eav - rGeph G domain 462-623 – Arabidopsis thaliana

ReferencesReferences

↑ Tyagarajan SK, Fritschy JM. Gephyrin: a master regulator of neuronal function? Nat Rev Neurosci. 2014 Mar;15(3):141-56. doi: 10.1038/nrn3670. PMID:24552784 doi:http://dx.doi.org/10.1038/nrn3670
↑ Hales CM, Rees H, Seyfried NT, Dammer EB, Duong DM, Gearing M, Montine TJ, Troncoso JC, Thambisetty M, Levey AI, Lah JJ, Wingo TS. Abnormal gephyrin immunoreactivity associated with Alzheimer disease pathologic changes. J Neuropathol Exp Neurol. 2013 Nov;72(11):1009-15. doi:, 10.1097/01.jnen.0000435847.59828.db. PMID:24128675 doi:http://dx.doi.org/10.1097/01.jnen.0000435847.59828.db
↑ Maric HM, Kasaragod VB, Haugaard-Kedstrom L, Hausrat TJ, Kneussel M, Schindelin H, Stromgaard K. Design and Synthesis of High-Affinity Dimeric Inhibitors Targeting the Interactions between Gephyrin and Inhibitory Neurotransmitter Receptors. Angew Chem Int Ed Engl. 2014 Nov 20. doi: 10.1002/anie.201409043. PMID:25413248 doi:http://dx.doi.org/10.1002/anie.201409043

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky

[1] Tyagarajan SK, Fritschy JM. Gephyrin: a master regulator of neuronal function? Nat Rev Neurosci. 2014 Mar;15(3):141-56. doi: 10.1038/nrn3670. PMID:24552784 doi:http://dx.doi.org/10.1038/nrn3670

[2] Hales CM, Rees H, Seyfried NT, Dammer EB, Duong DM, Gearing M, Montine TJ, Troncoso JC, Thambisetty M, Levey AI, Lah JJ, Wingo TS. Abnormal gephyrin immunoreactivity associated with Alzheimer disease pathologic changes. J Neuropathol Exp Neurol. 2013 Nov;72(11):1009-15. doi:, 10.1097/01.jnen.0000435847.59828.db. PMID:24128675 doi:http://dx.doi.org/10.1097/01.jnen.0000435847.59828.db

[3] Maric HM, Kasaragod VB, Haugaard-Kedstrom L, Hausrat TJ, Kneussel M, Schindelin H, Stromgaard K. Design and Synthesis of High-Affinity Dimeric Inhibitors Targeting the Interactions between Gephyrin and Inhibitory Neurotransmitter Receptors. Angew Chem Int Ed Engl. 2014 Nov 20. doi: 10.1002/anie.201409043. PMID:25413248 doi:http://dx.doi.org/10.1002/anie.201409043

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[2]

[3]

@@ Line 1: / Line 1: @@
-<StructureSection load='4u91' size='340' side='right' caption='Rat gephyrin E domain (cyan) complex with glycine receptor peptide (magenta and violet), acetate and Ca+2 ion (green) (PDB code [[4u91]])' scene='80/800120/Cv/4'>
+<StructureSection load='4u91' size='340' side='right' caption='Rat gephyrin E domain (cyan) complex with glycine receptor peptides (magenta and pink), acetate and Ca+2 ion (green) (PDB code [[4u91]])' scene='80/800120/Cv/4'>
 == Function ==
@@ Line 11: / Line 11: @@
 == Structural highlights ==
-Glycine receptor peptides interacts with several side chains of Gep<ref>PMID:25413248</ref>.
+<scene name='80/800120/Cv/5'>Para-Phenyl crosslinked Glycine receptor beta subunit derived dimeric peptide</scene> interacts with <scene name='80/800120/Cv/8'>several side chains of Gep</scene><ref>PMID:25413248</ref>.
+*<scene name='80/800120/Cv/7'>1,1'-benzene-1,4-diylbis(1H-pyrrole-2,5-dione) crosslinking with peptides</scene>
@@ Line 22: / Line 23: @@
 [[2fu3]], [[5erq]], [[4pd0]] - rGeph E domain 318-736 - rat<br />
 [[2fts]], [[4pd1]], [[1t3e]], [[4u91]] - rGeph E domain + glycine receptor peptide<br />
+[[6hso]] - rGeph E domain + glycine receptor peptide + ADP<br /
 [[4tk1]], [[4tk2]], [[4tk3]], [[4tk4]], [[4u90]] - rGeph E domain + GABA receptor peptide<br />
+[[6hsn]] - rGeph E domain + GABA receptor peptide + ADP<br />
 [[5ers]] - rGeph E domain + AMP<br />
 [[5ert]], [[5err]] - rGeph E domain + ADP<br />
 [[5eru]] - rGeph E domain + ADP + Mo + MoO4<br />
 [[5erv]] - rGeph E domain + ADP + W + WO4<br />
-[[1thc]] - rGeph N terminal<br />
+[[6fgc]] - rGeph E domain + artesunate + ADP<br />
+[[6fgd]] - rGeph E domain + artemether + ADP<br />
+[[1ihc]], [[1jlj]] - rGeph N terminal<br />
+[[1eav]] - rGeph G domain 462-623 – ''Arabidopsis thaliana''<br />
 == References ==