PDBsum entry 4kfm

Metal transport

PDB id: 4kfm

Contents

Protein chains

328 a.a.

339 a.a.

60 a.a.

Ligands

PIO

LMT

Metals

__K ×5

_NA

PDB id:

4kfm

Name:

Metal transport

Title:

Crystal structure of the g protein-gated inward rectifier k+ channel girk2 (kir3.2) in complex with the beta-gamma g protein subunits

Structure:

G protein-activated inward rectifier potassium channel 2. Chain: a. Engineered: yes. Guanine nucleotide-binding protein g(i)/g(s)/g(t) subunit beta-1. Chain: b. Synonym: transducin beta chain 1. Engineered: yes. Guanine nucleotide-binding protein g(i)/g(s)/g(o) subunit

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: kcnj6. Expressed in: pichia pastoris. Expression_system_taxid: 4922. Homo sapiens. Human. Organism_taxid: 9606.

Resolution:

3.45Å R-factor: 0.230 R-free: 0.265

Authors:

M.R.Whorton,R.Mackinnon

Key ref:

M.R.Whorton and R.MacKinnon (2013). X-ray structure of the mammalian GIRK2-βγ G-protein complex. Nature, 498, 190-197. PubMed id: 23739333 DOI: 10.1038/nature12241

Date:

27-Apr-13 Release date: 12-Jun-13

Protein chain

P48542  (KCNJ6_MOUSE) -  G protein-activated inward rectifier potassium channel 2 from Mus musculus

Seq: 425 a.a.

Struc: 328 a.a.*

Protein chain

P62873  (GBB1_HUMAN) -  Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 from Homo sapiens

Seq: 340 a.a.

Struc: 339 a.a.

Protein chain

P59768  (GBG2_HUMAN) -  Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 from Homo sapiens

Seq: 71 a.a.

Struc: 60 a.a.

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

DOI no: 10.1038/nature12241

Nature 498:190-197 (2013)

PubMed id: 23739333

X-ray structure of the mammalian GIRK2-βγ G-protein complex.

M.R.Whorton, R.MacKinnon.

ABSTRACT

G-protein-gated inward rectifier K(+) (GIRK) channels allow neurotransmitters, through G-protein-coupled receptor stimulation, to control cellular electrical excitability. In cardiac and neuronal cells this control regulates heart rate and neural circuit activity, respectively. Here we present the 3.5 Å resolution crystal structure of the mammalian GIRK2 channel in complex with βγ G-protein subunits, the central signalling complex that links G-protein-coupled receptor stimulation to K(+) channel activity. Short-range atomic and long-range electrostatic interactions stabilize four βγ G-protein subunits at the interfaces between four K(+) channel subunits, inducing a pre-open state of the channel. The pre-open state exhibits a conformation that is intermediate between the closed conformation and the open conformation of the constitutively active mutant. The resultant structural picture is compatible with 'membrane delimited' activation of GIRK channels by G proteins and the characteristic burst kinetics of channel gating. The structures also permit a conceptual understanding of how the signalling lipid phosphatidylinositol-4,5-bisphosphate (PIP2) and intracellular Na(+) ions participate in multi-ligand regulation of GIRK channels.