4F8A

Cyclic nucleotide binding-homology domain from mouse EAG1 potassium channel

Summary for 4F8A

• Entry DOI: 10.2210/pdb4f8a/pdb
• Descriptor: Potassium voltage-gated channel subfamily H member 1 (2 entities in total)
• Functional Keywords: probable regulatory domain of potassium channel, membrane protein, transport protein
• Biological source: Mus musculus (mouse)
• Cellular location: Cell membrane (By similarity); Multi-pass membrane protein: Q60603
• Total number of polymer chains: 1
• Total formula weight: 18019.87

Authors

Marques-Carvalho, M.J.,Sahoo, N.,Muskett, F.W.,Vieira-Pires, R.S.,Gabant, G.,Cadene, M.,Schonherr, R.,Morais-Cabral, J.H. (deposition date: 2012-05-17, release date: 2012-07-11, Last modification date: 2024-02-28)

Primary citation

Marques-Carvalho, M.J.,Sahoo, N.,Muskett, F.W.,Vieira-Pires, R.S.,Gabant, G.,Cadene, M.,Schonherr, R.,Morais-Cabral, J.H.
Structural, Biochemical, and Functional Characterization of the Cyclic Nucleotide Binding Homology Domain from the Mouse EAG1 Potassium Channel.
J.Mol.Biol., 423:34-46, 2012

PubMed Abstract: KCNH channels are voltage-gated potassium channels with important physiological functions. In these channels, a C-terminal cytoplasmic region, known as the cyclic nucleotide binding homology (CNB-homology) domain displays strong sequence similarity to cyclic nucleotide binding (CNB) domains. However, the isolated domain does not bind cyclic nucleotides. Here, we report the X-ray structure of the CNB-homology domain from the mouse EAG1 channel. Through comparison with the recently determined structure of the CNB-homology domain from the zebrafish ELK (eag-like K(+)) channel and the CNB domains from the MlotiK1 and HCN (hyperpolarization-activated cyclic nucleotide-gated) potassium channels, we establish the structural features of CNB-homology domains that explain the low affinity for cyclic nucleotides. Our structure establishes that the "self-liganded" conformation, where two residues of the C-terminus of the domain are bound in an equivalent position to cyclic nucleotides in CNB domains, is a conserved feature of CNB-homology domains. Importantly, we provide biochemical evidence that suggests that there is also an unliganded conformation where the C-terminus of the domain peels away from its bound position. A functional characterization of this unliganded conformation reveals a role of the CNB-homology domain in channel gating.

PubMed: 22732247
DOI: 10.1016/j.jmb.2012.06.025

Experimental method

X-RAY DIFFRACTION (2.2 Å)