PDBsum entry 6l6f

Membrane protein

PDB id: 6l6f

Contents

Protein chains

715 a.a.

PDB id:

6l6f

Name:

Membrane protein

Title:

Gluk3 receptor complex with ubp301

Structure:

Glutamate receptor ionotropic, kainate 3. Chain: a, b, c, d. Synonym: glutamate receptor,ionotropic,kainate 3,isoform cra_b. Engineered: yes. Mutation: yes

Source:

Rattus norvegicus. Rat. Organism_taxid: 10116. Gene: grik3, rcg_30794. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek 293 gnti-.

Authors:

J.Kumar,J.Kumari,A.P.Burada

Key ref:

J.Kumari et al. (2020). Structural dynamics of the GluK3-kainate receptor neurotransmitter binding domains revealed by cryo-EM. Int J Biol Macromol, 149, 1051-1058. PubMed id: 32006583 DOI: 10.1016/j.ijbiomac.2020.01.282

Date:

28-Oct-19 Release date: 04-Mar-20

Protein chains

P42264  (GRIK3_RAT) -  Glutamate receptor ionotropic, kainate 3 from Rattus norvegicus

Seq: 919 a.a.

Struc: 715 a.a.*

* PDB and UniProt seqs differ at 6 residue positions (black crosses)

DOI no: 10.1016/j.ijbiomac.2020.01.282

Int J Biol Macromol 149:1051-1058 (2020)

PubMed id: 32006583

Structural dynamics of the GluK3-kainate receptor neurotransmitter binding domains revealed by cryo-EM.

J.Kumari, A.D.Bendre, S.Bhosale, R.Vinnakota, A.P.Burada, G.Tria, R.B.G.Ravelli, P.J.Peters, M.Joshi, J.Kumar.

ABSTRACT

Kainate receptors belong to the ionotropic glutamate receptor family and play critical roles in the regulation of synaptic networks. The kainate receptor subunit GluK3 has unique functional properties and contributes to presynaptic facilitation at the hippocampal mossy fiber synapses along with roles at the post-synapses. To gain structural insights into the unique functional properties and dynamics of GluK3 receptor, we imaged them via electron microscopy in the apo-state and in complex with either agonist kainate or antagonist UBP301. Our analysis of all the GluK3 full-length structures not only provides insights into the receptor transitions between desensitized and closed states but also reveals a "non-classical" conformation of neurotransmitter binding domain in the closed-state distinct from that observed in AMPA and other kainate receptor structures. We show by molecular dynamics simulations that Asp759 influences the stability of the LBD dimers and hence could be responsible for the observed conformational variability and dynamics of the GluK3 via electron microscopy. Lower dimer stability could explain faster desensitization and low agonist sensitivity of GluK3. In overview, our work helps to associate biochemistry and physiology of GluK3 receptors with their structural biology and offers structural insights into the unique functional properties of these atypical receptors.