PDBsum entry 1kpl

Membrane protein

PDB id: 1kpl

Contents

Protein chains

430 a.a. *

Ligands

SO4 ×4

OCT ×2

MYS ×2

Metals

_CL ×4

Waters ×2

* Residue conservation analysis

References listed in PDB file

Key reference

Title

X-Ray structure of a clc chloride channel at 3.0 a reveals the molecular basis of anion selectivity.

Authors

R.Dutzler, E.B.Campbell, M.Cadene, B.T.Chait, R.Mackinnon.

Ref.

Nature, 2002, 415, 287-294. [DOI no: 10.1038/415287a]

PubMed id

11796999

Abstract

The ClC chloride channels catalyse the selective flow of Cl- ions across cell membranes, thereby regulating electrical excitation in skeletal muscle and the flow of salt and water across epithelial barriers. Genetic defects in ClC Cl- channels underlie several familial muscle and kidney diseases. Here we present the X-ray structures of two prokaryotic ClC Cl- channels from Salmonella enterica serovar typhimurium and Escherichia coli at 3.0 and 3.5 A, respectively. Both structures reveal two identical pores, each pore being formed by a separate subunit contained within a homodimeric membrane protein. Individual subunits are composed of two roughly repeated halves that span the membrane with opposite orientations. This antiparallel architecture defines a selectivity filter in which a Cl- ion is stabilized by electrostatic interactions with alpha-helix dipoles and by chemical coordination with nitrogen atoms and hydroxyl groups. These findings provide a structural basis for further understanding the function of ClC Cl- channels, and establish the physical and chemical basis of their anion selectivity.

Figure 2.
Figure 2: Experimental electron density. a, F[Se] - F[native] difference density (contoured at 4 ) in the EcClC P2[1]2[1]2[1] crystal form superimposed on an carbon trace of the EcClC subunit viewed from outside the cell. Side chains of methionine residues are shown in stick representation with the position of the Se atom indicated by a green sphere. The difference Fourier map was calculated to 4.0 Å and averaged over the six subunits in the asymmetric unit. b, Electron density map from the StClC P2[1] crystal form at 3.0 Å resolution, contoured at 1 . The map was calculated from native amplitudes and solvent-flattened, averaged phases. The refined structure is shown as a stick model. Figures 2 -6 were prepared with DINO (http://www.dino3d.org).

Figure 7.
Figure 7: Two architectures for ion-channel proteins. a, The antiparallel architecture of ClC Cl- channels contains structurally similar halves with opposite orientations in the membrane (arrows). This architecture permits like ends (same dipole sense) of -helices to point at the membrane centre from opposite sides of the membrane (180° separation). b, The parallel or barrel stave architecture of K+ channels contains structurally similar or identical subunits with the same membrane orientation (arrows). Helices point at the membrane centre from the same side of the membrane. Helices are depicted as dipoles with blue (positive) and red (negative) ends.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2002, 415, 287-294) copyright 2002.