Biochemistry Seminar: Amedee des Georges, "Understanding allosteric coupling in ion channels using cryo-electron microscopy image classification techniques"
Mar 29, 2017
from 12:00 PM to 01:00 PM
|Where||CUNY ASRC Main Auditorium|
|Contact Name||Lauren Gohara|
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Cryo-electron microscopy (cryo-EM) is revolutionizing the structural biology of membrane proteins. It has allowed the structural study of long sought after targets, such as the type 1 ryanodine receptor (RyR1). But another very important advantage is that it allows to study the complex dynamics associated with membrane protein function.
The type-1 ryanodine receptor (RyR1) is an intracellular calcium (Ca2+) release channel required for skeletal muscle contraction. We used single-particle cryo-EM to study the dynamics of RyR1 in multiple functional states, revealing the conformational changes key to channel gating and ligand-dependent activation. The binding sites for the channel activators Ca2+, ATP and caffeine were identified and the conformational changes associated with their binding observed independently. Now, the advent of a new image analysis technique called manifold embedding allows to peer deeper into the complex dynamics and allosteric coupling of this 2MDa protein. I will discuss our current efforts at modeling its behavior and understanding its gating mechanism