PDBsum entry 4l11

Metal transport

PDB id: 4l11

Contents

Protein chain

198 a.a.

Waters ×18

PDB id:

4l11

Name:

Metal transport

Title:

Structure of thE C-linker/cnbhd of agerg channels

Structure:

Agap007709-pa. Chain: a. Fragment: c-linker/cnbhd (unp residues 535-734). Engineered: yes

Source:

Anopheles gambiae. African malaria mosquito. Organism_taxid: 7165. Gene: agap007709, agap_agap007709, erg. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.55Å R-factor: 0.221 R-free: 0.256

Authors:

T.I.Brelidze

Key ref:

T.I.Brelidze et al. (2013). Structure of the C-terminal region of an ERG channel and functional implications. Proc Natl Acad Sci U S A, 110, 11648-11653. PubMed id: 23801759 DOI: 10.1073/pnas.1306887110

Date:

01-Jun-13 Release date: 26-Jun-13

Protein chain

Q7QJX3  (Q7QJX3_ANOGA) -  AGAP007709-PA from Anopheles gambiae

Seq: 762 a.a.

Struc: 198 a.a.

DOI no: 10.1073/pnas.1306887110

Proc Natl Acad Sci U S A 110:11648-11653 (2013)

PubMed id: 23801759

Structure of the C-terminal region of an ERG channel and functional implications.

T.I.Brelidze, E.C.Gianulis, F.DiMaio, M.C.Trudeau, W.N.Zagotta.

ABSTRACT

The human ether-à-go-go-related gene (hERG) encodes a K(+) channel crucial for repolarization of the cardiac action potential. EAG-related gene (ERG) channels contain a C-terminal cyclic nucleotide-binding homology domain coupled to the pore of the channel by a C-linker. Here, we report the structure of the C-linker/cyclic nucleotide-binding homology domain of a mosquito ERG channel at 2.5-Å resolution. The structure reveals that the region expected to form the cyclic nucleotide-binding pocket is negatively charged and is occupied by a short β-strand, referred to as the intrinsic ligand, explaining the lack of direct regulation of ERG channels by cyclic nucleotides. In hERG channels, the intrinsic ligand harbors hereditary mutations associated with long-QT syndrome (LQTS), a potentially lethal cardiac arrhythmia. Mutations in the intrinsic ligand affected hERG channel gating and LQTS mutations abolished hERG currents and altered trafficking of hERG channels, which explains the LQT phenotype. The structure also reveals a dramatically different conformation of the C-linker compared with the structures of the related ether-à-go-go-like K(+) and hyperpolarization-activated cyclic nucleotide-modulated channels, suggesting that the C-linker region may be highly dynamic in the KCNH, hyperpolarization-activated cyclic nucleotide-modulated, and cyclic nucleotide-gated channels.