PDBsum entry: 1byw

Membrane protein

PDB id: 1byw

Contents

Protein chain

110 a.a. *

Waters ×27

* Residue conservation analysis

PDB id:

1byw

Name:

Membrane protein

Title:

Structure of the n-terminal domain of the human-erg potassium channel

Structure:

Protein (human erg potassium channel). Chain: a. Fragment: n-terminal domain. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cellular_location: cell membrane. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Dimer (from PQS)

Resolution:

2.60Å R-factor: 0.252 R-free: 0.286

Authors:

J.H.M.Cabral,A.Lee,R.Mackinnon

Key ref:

J.H.Morais Cabral et al. (1998). Crystal structure and functional analysis of the HERG potassium channel N terminus: a eukaryotic PAS domain. Cell, 95, 649-655. PubMed id: 9845367 DOI: 10.1016/S0092-8674(00)81635-9

Date:

15-Oct-98 Release date: 16-Dec-98

Protein chain

Q12809  (KCNH2_HUMAN) -  Potassium voltage-gated channel subfamily H member 2

Seq: 1159 a.a.

Struc: 110 a.a.*

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

 Gene Ontology (GO) functional annotation 

• Biological process: signal transduction (3 terms)
• Biochemical function: signal transducer activity (2 terms)

DOI no: 10.1016/S0092-8674(00)81635-9

Cell 95:649-655 (1998)

PubMed id: 9845367

Crystal structure and functional analysis of the HERG potassium channel N terminus: a eukaryotic PAS domain.

J.H.Morais Cabral, A.Lee, S.L.Cohen, B.T.Chait, M.Li, R.Mackinnon.

ABSTRACT

The HERG voltage-dependent K+ channel plays a role in cardiac electrical excitability, and when defective, it underlies one form of the long QT syndrome. We have determined the crystal structure of the HERG K+ channel N-terminal domain and studied its role as a modifier of gating using electrophysiological methods. The domain is similar in structure to a bacterial light sensor photoactive yellow protein and provides the first three-dimensional model of a eukaryotic PAS domain. Scanning mutagenesis of the domain surface has allowed the identification of a hydrophobic "hot spot" forming a putative interface with the body of the K+ channel to which it tightly binds. The presence of the domain attached to the channel slows the rate of deactivation. Given the roles of PAS domains in biology, we propose that the HERG N-terminal domain has a regulatory function.

Selected figure(s)

Figure 1.
Figure 1. Membrane-Spanning Topology and Current Recorded from HERG K^+ Channels(A) The HERG channel monomer has six transmembrane segments (blue) labeled S1 to S6; S4 is the voltage sensor, and it contains six positively charged amino acids as indicated by the + symbols. The channel has a large C terminus and the characteristic N-terminal eag domain (red), both cytosolic; the pore region is situated between S5 and S6. The functional channel is a tetramer with a central ion conduction pathway.(B) Upon depolarization of the cell membrane to 10 mV from a holding voltage of −80 mV, the channels activate, passing from the closed state C to the open state O* (the * symbol indicates a conducting state) and ionic current is observed in the outward direction. Only a small amount of current is observed because the channels quickly enter the I (inactivated) state, which does not conduct ions. When the membrane is repolarized to −110 mV, the channels pass from the I state to the open state O* and a large inward “tail” current is recorded. This current slowly decays with an increasing number of channels deactivating or returning to the closed state C.

Figure 3.
Figure 3. The eag Domain Confers Wild-Type Gating Properties(A) Tail currents were recorded from oocytes expressing truncated HERG channels 3 and 24 hr after protein injection of eag domain protein. Currents from wild-type and truncated HERG are shown for comparison. The voltage protocol used is the same as in Figure 2A.(B) Scaled currents recorded at −110 mV are superimposed.

The above figures are reprinted by permission from Cell Press: Cell (1998, 95, 649-655) copyright 1998.

Figures were selected by an automated process.