Molecular Dynamics Simulation Study of the Cytosolic Mouth in Kcv-type Potassium Channels. (Articolo in rivista)

Type
Label
  • Molecular Dynamics Simulation Study of the Cytosolic Mouth in Kcv-type Potassium Channels. (Articolo in rivista) (literal)
Anno
  • 2007-01-01T00:00:00+01:00 (literal)
Alternative label
  • Tayefeh S., Kloss T., Thiel G., Hertel B., Moroni A., and Kast S.M. (2007)
    Molecular Dynamics Simulation Study of the Cytosolic Mouth in Kcv-type Potassium Channels.
    in Biochemistry (Easton)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Tayefeh S., Kloss T., Thiel G., Hertel B., Moroni A., and Kast S.M. (literal)
Pagina inizio
  • 4826 (literal)
Pagina fine
  • 4839 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 46 (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
Titolo
  • Molecular Dynamics Simulation Study of the Cytosolic Mouth in Kcv-type Potassium Channels. (literal)
Abstract
  • The functional effect of mutations near the intracellular mouth of the short viral Kcv potassium channel was studied by molecular dynamics simulations. As a model system we used the analogously mutated and truncated KirBac1.1, a channel with known crystal structure that shares genuine local sequence motifs with Kcv. By a novel simulated annealing methodology for structural averaging, information about the structure and dynamics of the intracellular mouth was extracted and complemented by Poisson-Boltzmann and 3D-RISM (reference interaction site model) integral equation theory for the determination of the K+ free energy surface. Besides the wild-type analogue of Kcv with its experimental reference activity (truncated KirBac1.1), two variants were studied: a deletion mutant where the N-terminus is further truncated by eight amino acids, showing inactivity in the Kcv reference system, and a point mutant where the kink-forming proline at position 13 is substituted by alanine, resulting in hyperactivity. The computations reveal that the change of activity is closely related to a hydrophilic intracellular constriction formed by the C-terminal residues of the monomers. Hyperactivity of the point mutant is correlated with both sterical and electrostatic factors, while inactivity of the deletion mutant is related to a loss of specific salt bridge patterns between the C- and N-terminus at the constriction and to the consequences for ion passage barriers, as revealed by integral equation theory. The cytosolic gate, however, is probably formed by the N-terminal segment up to the proline kink and not by the constriction. The results are compared with design principles found for other channels. (literal)
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