PDBsum entry 1a68

Potassium channels

PDB id: 1a68

Contents

Protein chain

87 a.a.

Waters ×35

References listed in PDB file

Key reference

Title

Crystal structure of the tetramerization domain of the shaker potassium channel.

Authors

A.Kreusch, P.J.Pfaffinger, C.F.Stevens, S.Choe.

Ref.

Nature, 1998, 392, 945-948. [DOI no: 10.1038/31978]

PubMed id

9582078

Abstract

Voltage-dependent, ion-selective channels such as Na+, Ca2+ and K+ channel proteins function as tetrameric assemblies of identical or similar subunits. The clustering of four subunits is thought to create an aqueous pore centred at the four-fold symmetry axis. The highly conserved, amino-terminal cytoplasmic domain (approximately 130 amino acids) immediately preceding the first putative transmembrane helix S1 is designated T1. It is known to confer specificity for tetramer formation, so the heteromeric assembly of K+-channel subunits is an important mechanism for the observed channel diversity. We have determined the crystal structure of the T1 domain of a Shaker potassium channel at 1.55 A resolution. The structure reveals that four identical subunits are arranged in a four-fold symmetry surrounding a centrally located pore about 20 A in length. Subfamily-specific assembly is provided primarily by polar interactions encoded in a conserved set of amino acids at its tetramerization interface. Most highly conserved amino acids in the T1 domain of all known potassium channels are found in the core of the protein, indicating a common structural framework for the tetramer assembly.

Figure 2.
Figure 2 T1 tetramer a, Stereo side-view of the T1 tetramer. Only three subunits of the tetramer are shown; the frontmost subunit is omitted for clarity. The four-fold symmetry axis is vertical. Layers 1, 2 and 3 in each subunit are shown in green, blue and red, respectively, starting from the N terminus at the putative cytoplasmic side. The -helical and -sheet segments are labelled as in Fig. 1b. All figures except Figs 1 and 2c have been prepared using SETOR29. b, Stereo view of the T1 tetramer from the N-terminal side along the four-fold axis, which passes through the centre of the tetramer. c, Molecular surface representation of the T1 tetramer. Electrostatic potential calculated by GRASP30 is colour coded on the surface from blue ( 10 kT) to red ( -7 kT). Left, side view as in a. Because of the symmetry, the surface visible on the subunit to the left of the pore interfaces with a surface on the omitted subunit, which is identical to the subunit surface visible on the right. Right, the T1 tetramer is viewed from the cytoplasmic side as in b. The narrowest opening ( 3.2 Å in diameter) in the centre of the pore (white region) is formed by side-chain atoms of N136.

Figure 3.
Figure 3 T1 side chains and views of layers 1, 2 and 3. a, Side chains conserved in all four subfamilies of voltage-gated potassium channels (those in black boxes in Fig. 1b). The backbone of the T1 subunit is shown as a ribbon. Subdomain A is inblue, the variable region between subdomains A and B is in red, and subdomain B is in green. b, Side chains of 15 residues involved in polar intersubunit interactions (E 78, T 79, Q 80, T 83, D 119, Q 126, R 130 and R 132 from subunit 1; N 71', S 73', R 76', D 112', R 115', D 140' and E 144' from subunit 2). Only side chain-side chain interactions are shown. Underlined residues are conserved in all Shaker subfamily members. c-e, Cross-sectional views of layers 1 (c), 2 (d) and 3 (e). C backbone atoms of the T1 tetramer in the three crystal forms (I in blue, C in green and P in red) are superimposed. Based on all main-chain atoms, the root mean square deviations are 0.92 Å between the P and C forms, 0.84 Å between the I and C forms, and 0.77 Å between the I and P forms. The most significant differences occur within the region between R 133 and D 140 (r.m.s. deviations between 1.25 and 2.1 Å).

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (1998, 392, 945-948) copyright 1998.