How proteins are degraded: from structures to kinetics

16 February 2018

Ying Lu
Department of Systems Biology
Harvard Medical School


Nearly every major process in a cell is carried out by large protein assemblies of 10 or more subunits. Recent advancement of cryo-electron microscopy technology greatly facilitates the resolution of their structures. Underlying their exquisite structural features are ordered chemical reactions coupled to conformational changes, most of which are still waiting to be revealed to understand how those structural complexities become necessary and sufficient for fulfilling their biological functions.

The ubiquitin-mediated protein degradation plays a key role in most cellular functions that demand accurate and efficient removal of undesired proteins. Ubiquitylated proteins are recognized and cleaved by the 26S proteasome, which is a 2.6 MDa protein complex universal in eukaryotes. The regulatory potency of this protein degradation machinery relies on its elaborate structure which was revealed recently. We still do not understand how the ATP-driven conformational changes of the proteasome are organized and utilized to carry out accurate substrate recognition and processive translocation. I will take this opportunity to present our recent structural studies on the conformational changes of the proteasome, and ongoing efforts of using single-molecule kinetic analysis and mathematical modeling to understand the structural-functional relationship of this protein machine.

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