4YKI

Mnemiopsis leidyi ML032222a iGluR LBD glycine complex

Summary for 4YKI

• Entry DOI: 10.2210/pdb4yki/pdb
• Related: 4YKJ 4YKK 4YKP
• Descriptor: ML032222a iGluR, GLYCINE, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: membrane protein, glutamate receptor, ion channel
• Biological source: Mnemiopsis leidyi
• Total number of polymer chains: 2
• Total formula weight: 58193.62

Authors

Alberstein, R.G.,Mayer, M.L. (deposition date: 2015-03-04, release date: 2015-10-21, Last modification date: 2024-10-30)

Primary citation

Alberstein, R.,Grey, R.,Zimmet, A.,Simmons, D.K.,Mayer, M.L.
Glycine activated ion channel subunits encoded by ctenophore glutamate receptor genes.
Proc.Natl.Acad.Sci.USA, 112:E6048-E6057, 2015

PubMed Abstract: Recent genome projects for ctenophores have revealed the presence of numerous ionotropic glutamate receptors (iGluRs) in Mnemiopsis leidyi and Pleurobrachia bachei, among our earliest metazoan ancestors. Sequence alignments and phylogenetic analysis show that these form a distinct clade from the well-characterized AMPA, kainate, and NMDA iGluR subtypes found in vertebrates. Although annotated as glutamate and kainate receptors, crystal structures of the ML032222a and PbiGluR3 ligand-binding domains (LBDs) reveal endogenous glycine in the binding pocket, whereas ligand-binding assays show that glycine binds with nanomolar affinity; biochemical assays and structural analysis establish that glutamate is occluded from the binding cavity. Further analysis reveals ctenophore-specific features, such as an interdomain Arg-Glu salt bridge, present only in subunits that bind glycine, but also a conserved disulfide in loop 1 of the LBD that is found in all vertebrate NMDA but not AMPA or kainate receptors. We hypothesize that ctenophore iGluRs are related to an early ancestor of NMDA receptors, suggesting a common evolutionary path for ctenophores and bilaterian species, and suggest that future work should consider both glycine and glutamate as candidate neurotransmitters in ctenophore species.

PubMed: 26460032
DOI: 10.1073/pnas.1513771112

Experimental method

X-RAY DIFFRACTION (1.21 Å)