PDBsum entry 4tk3

Biosynthetic protein,structural protein

PDB id: 4tk3

Contents

Protein chains

418 a.a.

Ligands

PHE-SER-ILE-VAL-GLY-THR-LEU-TYR-PRO

PHE-SER-ILE-VAL-GLY-THR-LEU-TYR

Waters ×36

PDB id:

4tk3

Name:

Biosynthetic protein,structural protein

Title:

Geph e in complex with a gaba receptor alpha3 derived double mutant peptide in spacegroup p21212

Structure:

Gephyrin. Chain: a, b. Fragment: domain e (unp residues 344-762). Synonym: putative glycine receptor-tubulin linker protein. Engineered: yes. Gamma-aminobutyric acid receptor subunit alpha-3. Chain: c, d. Fragment: unp residues 396-406. Synonym: gaba(a) receptor subunit alpha-3.

Source:

Rattus norvegicus. Rat. Organism_taxid: 10116. Gene: gphn, gph. Expressed in: escherichia coli. Expression_system_taxid: 469008. Synthetic: yes. Organism_taxid: 10116

Resolution:

2.70Å R-factor: 0.231 R-free: 0.267

Authors:

V.B.Kasaragod,H.M.Maric,H.Schindelin

Key ref:

H.M.Maric et al. (2014). Molecular basis of the alternative recruitment of GABA(A) versus glycine receptors through gephyrin. Nat Commun, 5, 5767. PubMed id: 25531214 DOI: 10.1038/ncomms6767

Date:

25-May-14 Release date: 24-Dec-14

Protein chains

Q03555  (GEPH_RAT) -  Gephyrin from Rattus norvegicus

Seq: 768 a.a.

Struc: 418 a.a.

Enzyme reactions

• Enzyme class 2: E.C.2.10.1.1 - molybdopterin molybdotransferase.
• Reaction: adenylyl-molybdopterin + molybdate = Mo-molybdopterin + AMP + H⁺
• Cofactor: Zn(2+) or Mg(2+)
• Enzyme class 3: E.C.2.7.7.75 - molybdopterin adenylyltransferase.
• Reaction: molybdopterin + ATP + H⁺ = adenylyl-molybdopterin + diphosphate
• Cofactor: Mn(2+) or Mg(2+)

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1038/ncomms6767

Nat Commun 5:5767 (2014)

PubMed id: 25531214

Molecular basis of the alternative recruitment of GABA(A) versus glycine receptors through gephyrin.

H.M.Maric, V.B.Kasaragod, T.J.Hausrat, M.Kneussel, V.Tretter, K.Strømgaard, H.Schindelin.

ABSTRACT

γ-Aminobutyric acid type A and glycine receptors (GABAARs, GlyRs) are the major inhibitory neurotransmitter receptors and contribute to many synaptic functions, dysfunctions and human diseases. GABAARs are important drug targets regulated by direct interactions with the scaffolding protein gephyrin. Here we deduce the molecular basis of this interaction by chemical, biophysical and structural studies of the gephyrin-GABAAR α3 complex, revealing that the N-terminal region of the α3 peptide occupies the same binding site as the GlyR β subunit, whereas the C-terminal moiety, which is conserved among all synaptic GABAAR α subunits, engages in unique interactions. Thermodynamic dissections of the gephyrin-receptor interactions identify two residues as primary determinants for gephyrin's subunit preference. This first structural evidence for the gephyrin-mediated synaptic accumulation of GABAARs offers a framework for future investigations into the regulation of inhibitory synaptic strength and for the development of mechanistically and therapeutically relevant compounds targeting the gephyrin-GABAAR interaction.