2L0W

Solution NMR structure of the N-terminal PAS domain of HERG potassium channel


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

The N-Terminal Tail of hERG Contains an Amphipathic alpha-Helix That Regulates Channel Deactivation

Ng, C.A.Hunter, M.J.Perry, M.D.Mobli, M.Ke, Y.Kuchel, P.W.King, G.F.Stock, D.Vandenberg, J.I.

(2011) PLoS One 6: e16191-e16191

  • DOI: https://doi.org/10.1371/journal.pone.0016191
  • Primary Citation of Related Structures:  
    2L0W

  • PubMed Abstract: 

    The cytoplasmic N-terminal domain of the human ether-a-go-go related gene (hERG) K+ channel is critical for the slow deactivation kinetics of the channel. However, the mechanism(s) by which the N-terminal domain regulates deactivation remains to be determined. Here we show that the solution NMR structure of the N-terminal 135 residues of hERG contains a previously described Per-Arnt-Sim (PAS) domain (residues 26-135) as well as an amphipathic α-helix (residues 13-23) and an initial unstructured segment (residues 2-9). Deletion of residues 2-25, only the unstructured segment (residues 2-9) or replacement of the α-helix with a flexible linker all result in enhanced rates of deactivation. Thus, both the initial flexible segment and the α-helix are required but neither is sufficient to confer slow deactivation kinetics. Alanine scanning mutagenesis identified R5 and G6 in the initial flexible segment as critical for slow deactivation. Alanine mutants in the helical region had less dramatic phenotypes. We propose that the PAS domain is bound close to the central core of the channel and that the N-terminal α-helix ensures that the flexible tail is correctly orientated for interaction with the activation gating machinery to stabilize the open state of the channel.


  • Organizational Affiliation

    Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Potassium voltage-gated channel, subfamily H (Eag-related), member 2, isoform CRA_b138Homo sapiensMutation(s): 0 
Gene Names: KCNH2hCG_18699
UniProt & NIH Common Fund Data Resources
Find proteins for Q12809 (Homo sapiens)
Explore Q12809 
Go to UniProtKB:  Q12809
PHAROS:  Q12809
GTEx:  ENSG00000055118 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ12809
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-01-26
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2020-02-26
    Changes: Data collection, Database references, Other
  • Version 1.3: 2023-06-14
    Changes: Database references, Other