Monday, April 11, 2016

ChemBio Seminar Series | "High Resolution CryoEM Structural Analysis of Heterogeneous Macromolecular Machines"

Thursday, April 14, 2016, 12:30pm in the Seaver Science Auditorium
SSL next to the library

Dr. Dmitry Lyumkis
Salk Helmsley Fellow, Laboratory of Genetics
The Salk Institute for Biological Studies

Single particle cryo-electron microscopy (cryoEM) is becoming a fundamental component of a
structural biologist’s toolkit, as improvements in instrumentation, software, automation, and
specimen preparation are making this technique increasingly powerful for the analysis of
macromolecules and macromolecular complexes. One of the primary advantages of the
methodology is the ability to analyze heterogeneous macromolecular assemblies, i.e. those that
exhibit either conformational mobility within distinct regions or compositional heterogeneity
exhibited by loosely and sub-stoichiometrically associated components. By employing
classification techniques, it is possible to place each individual particle image into one of several,
potentially many, groups, according to homogeneity. I will present three biological stories, which
center around and build upon the principles of high resolution cryoEM imaging and heterogeneity
analysis, each differing in the level of structural complexity. First, I will describe our structural
insights into a novel architecture of a retroviral integration complex called an intasome. I will then
describe how we used cryoEM to solve the structure of a very small protein complex by cryoEM
standards (150 kDa) to near-atomic resolution, wherein, crucially, we teased out the functionally
relevant enzymatic form using just 2% of the data. Finally, I will describe our current efforts
toward understanding the structural complexity and dynamic assembly underlying ribosome

The scientific community is invited to attend.

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