Construction and validation of a homology model of the human voltage-gated proton channel hH V 1

  • Kethika Kulleperuma, Susan M.E. Smith, Deri Morgan, Boris Musset, John Holyoake, Nilmadhab Chakrabarti, Vladimir V. Cherny, Thomas E. DeCoursey, Régis Pomès
  • The Journal of General Physiology, March 2013, Rockefeller University Press
  • DOI: 10.1085/jgp.201210856

What is it about?

We evaluate two open-state models of hHV1, using extensive molecular dynamics simulations and experiment. Both approaches lead to a model with an open-state salt bridge between Asp112 and Arg208. The first Arg partakes in an external charge cluster; the third in an internal cluster. If proton channels were content to mimic other voltage-gated channels, they might move all three S4 Arg residues from internal to external vestibules. But instead they opt for a stable open state!

Why is it important?

This model implies that the S4 segment moves a much shorter distance during channel opening than was previously believed. This idea was strongly supported by a recent EPR study by Li et al (PNAS, 2015).

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The following have contributed to this page: Professor Thomas E DeCoursey