Nuclear Magnetic Resonance Solution Structure and
Functional Behavior of the Human Proton Channel
Posted on 2019-09-21 - 12:03
The human voltage-gated
proton channel [Hv1(1) or VSDO(2)] plays an
important role in the human innate immune system.
Its structure differs considerably from those of other cation channels.
It is built solely of a voltage-sensing domain and thus lacks the
central pore domain, which is essential for other cation channels.
Here, we determined the solution structure of an N- and C-terminally
truncated human Hv1 (Δ-Hv1) in the resting state by nuclear
magnetic resonance (NMR) spectroscopy. Δ-Hv1 comprises the typical
voltage-sensing antiparallel four-helix bundle (S1–S4) preceded
by an amphipathic helix (S0). The solution structure corresponds to
an intermediate state between resting and activated forms of voltage-sensing
domains. Furthermore, Zn2+-induced closing of proton channel
Δ-Hv1 was studied with two-dimensional NMR spectroscopy, which
showed that characteristic large scale dynamics of open Δ-Hv1
are absent in the closed state of the channel. Additionally, pH titration
studies demonstrated that a higher H+ concentration is
required for the protonation of side chains in the Zn2+-induced closed state than in the open state. These observations
demonstrate both structural and dynamical changes involved in the
process of voltage gating of the Hv1 channel and, in the future, may
help to explain the unique properties of unidirectional conductance
and the exceptional ion selectivity of the channel.
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Bayrhuber, Monika; Maslennikov, Innokentiy; Kwiatkowski, Witek; Sobol, Alexander; Wierschem, Christoph; Eichmann, Cédric; et al. (2019). Nuclear Magnetic Resonance Solution Structure and
Functional Behavior of the Human Proton Channel. ACS Publications. Collection. https://doi.org/10.1021/acs.biochem.9b00471