Robert M Stroud
University of California, San Francisco, USA
Title: How do Voltage sensors in Transmembrane Channels Work?
Biography
Biography: Robert M Stroud
Abstract
The structure determination of an integral membrane protein complex of an ion regulated, voltage gated two-pore channel TPC-1 is reported at 2.9Å resolution. The channel is gated by external Ca++ ions and by voltage such that at zero voltage the channel is closed, in its resting state. In other voltage gated channels the sensor is activated leading to a comparison of the two states that provides the first example of what kinds of transitions occur in an inactive-to-active state in a voltage sensitive channel. This leads to a proposal for the mechanism of voltage sensors that control channel activity. In addition the channel controls an intracellular organelle that controls viral entry into cells for membrane encapsulated filoviruses. An inhibitor NED19 is bound that shows how the channel is inhibited allosterically, at a distance from the channel. Inhibition of TPC1 by NED19 leads to a cure for Ebola infected mice.
