Crina Nimigean, Prof. of Physiology & Biophysics in Anesthesiology; Prof. of Biochemistry & Biophysics at Weill Cornell Medicine, New York, will give a talk on "Mechanism of Lipid Modulation in Ion Channels."

This seminar will also be available by Zoom. Zoom link: https://gc-cuny.zoom.us/j/96975997619?pwd=C4JXA4s7H3L4sgnmmpWmoHdCunxLbe.1

Meeting ID: 969 7599 7619. Passcode: asrc**ccny

Please note: 

* Full names must be used to be admitted to the Zoom meeting.

* The Zoom meeting will be closed and locked at 12:15 p.m., and no one will be able to enter the meeting after that time.

ABSTRACT

Membrane proteins are continuously exposed to the complex lipid environment of cellular membranes, yet how specific lipids regulate their function remains poorly understood. In this talk, I will discuss two examples illustrating how membrane lipids tune ion-channel activity through defined structural mechanisms.

First, I will describe how lipids regulate temperature sensitivity in SthK, a bacterial ion channel that is activated by cold temperatures. We find that a functionally important, state-dependent intersubunit salt bridge acts as a temperature sensor, while lipid binding tunes temperature sensitivity by modulating the strength of this interaction. These findings suggest a general mechanism by which thermosensitivity can emerge from the interplay between protein energetics and the membrane environment.

Second, I will discuss regulation of rod photoreceptor cyclic nucleotide-gated (CNG) channels by the signaling lipid PI(4,5)P2 (PIP2). Although PIP2 was known to inhibit CNG channels, its very low abundance in rod outer segments raised questions about the physiological relevance of this effect. We show that PIP2 potently inhibits CNG channels at physiologically relevant concentrations (<0.2 mol%) and identify its binding site and mechanism of action. PIP2 binds to an allosteric site that stabilizes the closed channel and impedes conformational changes required for opening. Identification of this regulatory site also reveals a potential target for pharmacological modulation of CNG channels.

Together, these studies demonstrate how specific lipid–protein interactions can reshape the energetic landscape of ion channels to control physiologically important aspects of their function.