February 26, 2021Communications BiologyOpen Access

Specific PIP2 binding promotes calcium activation of TMEM16A chloride channels

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Why the study?

High-resolution TMEM16A structures failed to reveal an activated state with an unobstructed permeation pathway even with saturating Ca2+, leaving molecular mechanisms of gating and regulation poorly understood.

Population

TMEM16A channels

Comparison

Specific binding of PIP2 to TMEM16A in the Ca2+-bound state

Design

Atomistic simulations

Authors

ZJZhiguang JiaUniversity of Massachusetts Amherst JCJianhan ChenUniversity of Massachusetts Amherst

Discussion

Member takes

Implication

PIP2 binding enables spontaneous pore opening in Ca2+-bound TMEM16A simulations; leaves open the structural basis of physiological activation pending experimental validation.

Structured PICO

Population

Atomistic simulations of TMEM16A chloride channels

Intervention

Specific binding of PIP2 in the Ca2+-bound state

Outcome

Spontaneous opening of the permeation pathway and maximal Cl- conductance

Atomistic simulations reveal that PIP2 binding is required for the spontaneous opening of the TMEM16A chloride channel permeation pathway in the presence of calcium.

Cite This Study

Jia et al. (2021) studied this question.

synapsesocial.com/papers/6a72d4b79da973292f087206 https://doi.org/10.1038/s42003-021-01782-2

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Implication

PIP2 binding enables spontaneous pore opening in Ca2+-bound TMEM16A simulations; leaves open the structural basis of physiological activation pending experimental validation.