Original Publication Date
The Biophysical Journal
DOI of Original Publication
Date of Submission
Inwardly rectifying potassium (Kir) channels are characterized by a long pore comprised of continuous transmembrane and cytosolic portions. A high-resolution structure of a Kir3.1 chimera revealed the presence of the cytosolic (G-loop) gate captured in the closed or open conformations. Here, we conducted molecular-dynamics simulations of these two channel states in the presence and absence of phosphatidylinositol bisphosphate (PIP2), a phospholipid that is known to gate Kir channels. Simulations of the closed state with PIP2 revealed an intermediate state between the closed and open conformations involving direct transient interactions with PIP2, as well as a network of transitional inter- and intrasubunit interactions. Key elements in the G-loop gating transition involved a PIP2-driven movement of the N-terminus and C-linker that removed constraining intermolecular interactions and led to CD-loop stabilization of the G-loop gate in the open state. To our knowledge, this is the first dynamic molecular view of PIP2-induced channel gating that is consistent with existing experimental data.
From The Biophysical Journal, Meng, X-Y, Zhang, H-X, Logothetis, D.E., et al., The Molecular Mechanism by which PIP2 Opens the Intracellular G-Loop Gate of a Kir3.1 Channel, Vol. 102, Page 2049. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. Reprinted with permission.
Is Part Of
VCU Physiology and Biophysics Publications