PDBsum entry 6cnn

Membrane protein

PDB id: 6cnn

Contents

Protein chains

360 a.a.

146 a.a.

Ligands

POV ×4

LMT ×8

Metals

_CA ×12

__K ×4

PDB id:

6cnn

Name:

Membrane protein

Title:

Cryo-em structure of the human sk4/calmodulin channel complex in the ca2+ bound state i

Structure:

Intermediate conductance calcium-activated potassium channel protein 4. Chain: a, b, c, d. Synonym: sk4 channel, skca4, ikca1, ik1, kca3.1, kca4, putative gardos channel. Engineered: yes. Calmodulin-1. Chain: e, f, g, h. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: kcnn4, ik1, ikca1, kca4, sk4. Expressed in: homo sapiens. Expression_system_taxid: 9606. Gene: calm1, calm, cam, cam1. Expression_system_taxid: 9606

Authors:

C.H.Lee,R.Mackinnon

Key ref:

C.H.Lee and R.MacKinnon (2018). Activation mechanism of a human SK-calmodulin channel complex elucidated by cryo-EM structures. Science, 360, 508-513. PubMed id: 29724949 DOI: 10.1126/science.aas9466

Date:

08-Mar-18 Release date: 02-May-18

Protein chains

O15554  (KCNN4_HUMAN) -  Intermediate conductance calcium-activated potassium channel protein 4 from Homo sapiens

Seq: 427 a.a.

Struc: 360 a.a.

Protein chains

P0DP23  (CALM1_HUMAN) -  Calmodulin-1 from Homo sapiens

Seq: 149 a.a.

Struc: 146 a.a.

DOI no: 10.1126/science.aas9466

Science 360:508-513 (2018)

PubMed id: 29724949

Activation mechanism of a human SK-calmodulin channel complex elucidated by cryo-EM structures.

C.H.Lee, R.MacKinnon.

ABSTRACT

Small-conductance Ca²⁺-activated K⁺ (SK) channels mediate neuron excitability and are associated with synaptic transmission and plasticity. They also regulate immune responses and the size of blood cells. Activation of SK channels requires calmodulin (CaM), but how CaM binds and opens SK channels has been unclear. Here we report cryo-electron microscopy (cryo-EM) structures of a human SK4-CaM channel complex in closed and activated states at 3.4- and 3.5-angstrom resolution, respectively. Four CaM molecules bind to one channel tetramer. Each lobe of CaM serves a distinct function: The C-lobe binds to the channel constitutively, whereas the N-lobe interacts with the S4-S5 linker in a Ca²⁺-dependent manner. The S4-S5 linker, which contains two distinct helices, undergoes conformational changes upon CaM binding to open the channel pore. These structures reveal the gating mechanism of SK channels and provide a basis for understanding SK channel pharmacology.