PDBsum entry 4ykp

Membrane protein

PDB id: 4ykp

Contents

Protein chains

247 a.a.

Ligands

GLY-SER ×2

Metals

_MG

Waters ×743

PDB id:

4ykp

Name:

Membrane protein

Title:

Mnemiopsis leidyi ml032222a iglur lbd serine complex

Structure:

Ml032222a iglur. Chain: a, b. Fragment: ligand binding domain. Engineered: yes. Other_details: the construct contains residues k409-e526 and t682- s815 of the ml032222a ligand binding domain connected by a synthetic gt linker

Source:

Mnemiopsis leidyi. Organism_taxid: 27923. Gene: ml032222a. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.46Å R-factor: 0.138 R-free: 0.164

Authors:

R.G.Alberstein,M.L.Mayer

Key ref:

R.Alberstein et al. (2015). Glycine activated ion channel subunits encoded by ctenophore glutamate receptor genes. Proc Natl Acad Sci U S A, 112, E6048. PubMed id: 26460032 DOI: 10.1073/pnas.1513771112

Date:

04-Mar-15 Release date: 21-Oct-15

Protein chains

A0A0R4I973  (A0A0R4I973_MNELE) -  ML032222a iGluR from Mnemiopsis leidyi

Seq: 256 a.a.

Struc: 247 a.a.

DOI no: 10.1073/pnas.1513771112

Proc Natl Acad Sci U S A 112:E6048 (2015)

PubMed id: 26460032

Glycine activated ion channel subunits encoded by ctenophore glutamate receptor genes.

R.Alberstein, R.Grey, A.Zimmet, D.K.Simmons, M.L.Mayer.

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.