EMBL Keynote Lecture - Quality Control of Nascent Proteins, Ramanujan Hegde

Presenter: Ramanujan Hegde
MRC Laboratory of Molecular Biology, UK
From the EMBO Conference: Protein Synthesis and Translational Control
EMBL Advanced Training Centre Heidelberg, Germany
6 - 9 September 2017
The biogenesis of proteins involves a complex series of steps that include synthesis, targeting, modification, folding, and assembly. Failure at any of these steps results in the production of an aberrant product that must be degraded by the cell. An inability to promptly recognize or degrade aberrant proteins can lead to their accumulation, cell dysfunction, and in many cases, disease. Our group’s research efforts have focused on determining how the cell monitors each step in protein biosynthesis to identify failed products that are selectively targeted for degradation by the ubiquitin proteasome system. Using a primarily biochemical approach, we have been able to reconstitute several of these ubiquitination pathways including stalled translation products on the ribosome, mis-targeted membrane proteins, and orphan subunits of multi-protein complexes. Our studies are beginning to reveal the molecular logic of how nascent proteins are recognized by various cellular factors, and how the nature of these
interactions ultimately leads to a triage decision that segregates polypeptides between biosynthetic and degradative fates. These decisions are crucial for maintaining overall cellular homeostasis, and it is our hope that a molecular understanding of these pathways will provide new insights into the diseases caused by protein misfolding.

[@salaheddinehouache1015]

Amazing explanation