PDBsum entry: 1s33

Ion transport

PDB id: 1s33

Contents

Protein chains

97 a.a.

Metals

__K ×3

Waters ×111

Theoretical model

PDB id:

1s33

Name:

Ion transport

Title:

Kcsa potassium channel in a non-conducting state breaking the four-fold symmetry

Structure:

Voltage-gated potassium channel. Chain: a, b, c, d

Source:

Streptomyces lividans. Bacteria

Authors:

S.Berneche,B.Roux

Key ref:

S.Bernèche and B.Roux (2005). A gate in the selectivity filter of potassium channels. Structure, 13, 591-600. PubMed id: 15837197 DOI: 10.1016/j.str.2004.12.019

Date:

12-Jan-04 Release date: 19-Apr-05

Protein chain

Q54397  (KCSA_STRCO) -

DOI no: 10.1016/j.str.2004.12.019

Structure 13:591-600 (2005)

PubMed id: 15837197

A gate in the selectivity filter of potassium channels.

S.Bernèche, B.Roux.

ABSTRACT

The selectivity filter of potassium channels is the structural element directly responsible for the selective and rapid conduction of K+, whereas other parts of the protein are thought to function as a molecular gate that either permits or blocks the passage of ions. However, whether the selectivity filter itself also possesses the ability to play the role of a gate is an unresolved question. Using free energy molecular dynamics simulations, it is shown that the reorientation of two peptide linkages in the selectivity filter of the KcsA K+ channel can lead to a stable nonconducting conformational state. Two microscopic factors influence the transition toward such a conformational state: the occupancy of one specific cation binding site in the selectivity filter (S2), and the strength of intersubunit interactions involving the GYG signature sequence. These results suggest that such conformational transitions occurring in the selectivity filter might be related to different K+ channel gating events, including C-type (slow) inactivation.

Selected figure(s)

Figure 1.
Figure 1. Details of the Selectivity Filter of the KcsA K+ Channel
For clarity, only two of the four subunits are shown and some side chains are omitted. The dashed lines highlight the hydrogen bonds stabilizing the selectivity filter. Results from both X-ray crystallography (Morais-Cabral et al., 2001; Zhou et al., 2001) and molecular dynamics (MD) free energy simulations (Aqvist and Luzhvov, 2000; Bernèche and Roux, 2001) show that five specific cation binding sites, hereafter referred to as S[0] to S[4], are disposed along the narrow pore of the KcsA K+ channel. The figures in (A) and (B) correspond to the two main intermediate states that enable fast ion conduction with K+ in sites S[1] and S[3] (A) and in sites S[2] and S[4] (B). The latter configuration is enforced by the presence of a third cation, K+ or tetraethylammonium (TEA), in the binding site S[0] located at the extracellular end of the selectivity filter (Bernèche and Roux, 2001; Crouzy et al., 2001; Zhou et al., 2001; Thompson and Begenisich, 2003). The figures in (C) and (D) illustrate the conformational transition of the selectivity filter as observed in Bernèche and Roux (2000). The complete transition takes place in two steps, respectively involving the Val76-Gly77 (C) and Thr75-Val76 (D) amide planes in one of the four monomers. (C) In a first step, the carbonyl group of Val76 points away from the pore (indicated by an arrow). (D) In a second step, the carbonyl and side chain hydroxyl group (indicated by an arrow) of Thr75 closely coordinate the ion in S[3], while the amide group forms a strong hydrogen bond with the carbonyl group of Glu71 (dashed line). All molecular pictures were drawn with DINO (http://www.dino3d.org).

The above figure is reprinted by permission from Cell Press: Structure (2005, 13, 591-600) copyright 2005.

Figure was selected by the author.