Frontiers in Quantitative Biology Seminar
“Monitoring protein synthesis in time and space with ribosome profiling”
The Weissman laboratory is looking at how cells ensure that proteins fold into their correct shape, as well as the role of protein misfolding in disease and normal physiology. They are also developing experimental and analytical approaches for exploring the organizational principles of biological systems and globally monitoring protein translation through ribosome profiling.
Abstract:
I will talk about recent applications of ribosome profiling including: the identification of novel protein coding regions, demonstration of the principle of proportional synthesis of subunits in multiprotein complexes and monitoring localized protein translation using proximity-specific ribosome profiling.
I will also present our work on the identification and characterization of the ER membrane complex (EMC) and our functional studies establishing that the EMC is a general chaperone for the biogenesis of multipass membrane proteins. The endoplasmic reticulum (ER) supports biosynthesis of proteins with diverse transmembrane domain lengths and hydrophobicity. Imperfections in transmembrane domains such as charged residues in ion channels are often functionally important, but make co-translational membrane insertion and folding challenging. Our systematic proteomic approaches in both yeast and human cells revealed that the EMC binds to and promotes the biogenesis of a broad range of multipass transmembrane proteins. Proximity-specific ribosome profiling demonstrates that the EMC engages clients cotranslationally preferentially at imperfect transmembrane domains. The EMC can remain associated after completion of translation which both protects clients from premature proteasomal degradation and allows recruitment of substrate-specific and general chaperones. Thus the EMC broadly enables the biogenesis of multipass transmembrane proteins containing destabilizing features, thereby mitigating the trade off between function and stability.
March 22nd, 2018 at 2:15 PM in Clark Center Seminar Room S360
Frontiers in Quantitative Biology 2017/2018 Seminar Series
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