PDBsum entry 2nz0

Membrane protein

PDB id: 2nz0

Contents

Protein chains

170 a.a. *

136 a.a. *

Metals

_CA ×4

_ZN ×2

* Residue conservation analysis

PDB id:

2nz0

Name:

Membrane protein

Title:

Crystal structure of potassium channel kv4.3 in complex with its regulatory subunit kchip1

Structure:

Kv channel-interacting protein 1. Chain: a, c. Fragment: n-terminal deletion domain. Synonym: kchip1, a-type potassium channel modulatory protein 1, potassium channel-interacting protein 1, vesicle apc-binding protein. Engineered: yes. Potassium voltage-gated channel subfamily d member 3. Chain: b, d. Fragment: n-terminal domain (residues 6-145).

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: kchip1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Strain: k-12. Gene: kv4.3.

Resolution:

3.20Å R-factor: 0.265 R-free: 0.310

Authors:

H.Wang,Y.Yan,Y.Shen,L.Chen,K.Wang

Key ref:

H.Wang et al. (2007). Structural basis for modulation of Kv4 K+ channels by auxiliary KChIP subunits. Nat Neurosci, 10, 32-39. PubMed id: 17187064 DOI: 10.1038/nn1822

Date:

22-Nov-06 Release date: 26-Dec-06

Protein chains

Q9NZI2  (KCIP1_HUMAN) -  Kv channel-interacting protein 1 from Homo sapiens

Seq: 227 a.a.

Struc: 170 a.a.*

Protein chains

Q9UK17  (KCND3_HUMAN) -  Potassium voltage-gated channel subfamily D member 3 from Homo sapiens

Seq: 655 a.a.

Struc: 136 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: Chains A, B, C, D: E.C.?

DOI no: 10.1038/nn1822

Nat Neurosci 10:32-39 (2007)

PubMed id: 17187064

Structural basis for modulation of Kv4 K+ channels by auxiliary KChIP subunits.

H.Wang, Y.Yan, Q.Liu, Y.Huang, Y.Shen, L.Chen, Y.Chen, Q.Yang, Q.Hao, K.Wang, J.Chai.

ABSTRACT

KChIPs coassemble with pore-forming Kv4 alpha subunits to form a native complex in the brain and heart and regulate the expression and gating properties of Kv4 K(+) channels, but the mechanisms underlying these processes are unknown. Here we report a co-crystal structure of the complex of human Kv4.3 N-terminus and KChIP1 at a 3.2-A resolution. The structure reveals a unique clamping action of the complex, in which a single KChIP1 molecule, as a monomer, laterally clamps two neighboring Kv4.3 N-termini in a 4:4 manner, forming an octamer. The proximal N-terminal peptide of Kv4.3 is sequestered by its binding to an elongated groove on the surface of KChIP1, which is indispensable for the modulation of Kv4.3 by KChIP1, and the same KChIP1 molecule binds to an adjacent T1 domain to stabilize the tetrameric Kv4.3 channels. Taken together with biochemical and functional data, our findings provide a structural basis for the modulation of Kv4 by KChIPs.

Selected figure(s)

Figure 1.
Figure 1. The overall architecture of the KChIP1–Kv4.3N complex. All panels have the same color codes, with some secondary structural elements labeled specifically. (a) Schematic representation of the complex structure in one asymmetric unit. Two KChIP1 and two Kv4.3 molecules are shown in orange and blue, respectively. (b) The 4:4 complex of KChIP1-Kv4.3N shown was generated from the complex in a through symmetric operations. The complex in this panel has the same size as the one shown in Figure 6a. (c) One KChIP1 molecule interacts simultaneously with two Kv4.3Ns. In the complex, each KChIP1 molecule not only binds to the N-terminal peptide of one Kv4.3 but also interacts with an adjacent Kv4.3 T1 domain, forming two contact interfaces; the first interface is shown in the red frame and second interface is shown in the blue frame. (d) A cartoon of the KChIP1-Kv4.3N complex in 4:4 showing the clamping effect of KChIP1 molecule on the tetramer of Kv4.3.

Figure 6.
Figure 6. Comparison of the modeled Kv4.3-KChIP1 channel complex with Kv1.2-Kv 2. (a) Side views of Kv1.2–Kv4.3 T1-KChIP complex in which the Kv4.3 T1 domain fused with transmembrane-spanning domains of Kv1.2 (left) and Kv1.2-Kv 2 complex (right). The tetrameric subunits of Kv1.2 channels are labeled in cyan, yellow, pink and green, respectively. KChIP1 and Kv 2 are labeled in blue and wheat, respectively. (b) Top views of a, showing KChIPs positioned between two adjacent T1 domains (left) and Kv 2 beneath the T1 domains (right).

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Neurosci (2007, 10, 32-39) copyright 2007.

Figures were selected by the author.