Bil Clemons (Caltech)
March 1, 2017 - 12:00 pm
Thomas Laboratory 003
California Institute of Technology
Professor Bil Clemons received his PhD from the University of Utah working under Prof. Venki Ramakrishnan. During this time he spent two years as a visiting scientist at the Laboratory of Molecular Biology in Cambridge, England. The most notable achievement during his graduate work was that he was part of the team that solved the first atomic resolution structure of a small ribosomal subunit. This work led to a fundamental understanding of the translation of the genetic code and provided molecular details of the mechanism of a number of antibiotics. He then took a post-doctoral position at Harvard Medical School working for Profs. Tom Rapoport and Steve Harrison. During this time he solved the structure of the ubiquitous protein translocation channel. This membrane protein structure allowed for a clear model of how this fundamentally important complex could perform its unique function. Arriving at Caltech in 2006, the Clemons lab has continued its focus on structurally characterizing important biological systems.
Structural Insights into the Targeting of Tail-Anchored Membrane Proteins to the ER
Tail-anchor (TA) membrane proteins are an important and diverse class that are unable to be targeted via the co-translational SRP pathway. Instead, recent discoveries have identified factors directly involved in targeting these proteins to the ER. In yeast, these proteins form the GET pathway. Our lab has focused on structural and mechanistic studies of these proteins. The pathway as we posit begins with cytoplasmic chaperones that deliver the TA-proteins to Sgt2, which routes the proteins to Get3 via a Get4/Get5 hetero-tetramer. Get3 then forms a stable complex with the TA and delivers the proteins to the ER membrane. We have characterized these complexes using structural biology and biochemistry. I will frame a discussion of the pathway from our unique structural perspective including our recent insights into the more complicated mammalian system. For the human system, we demonstrate that the unique component Bag6 is not a canonical BAG protein and its TA targeting function can be localized to a minimal complex including a C-terminal fragment, Ubl4A and TRC35. This separates the targeting and degradation functions of Bag6 providing an explanation for some of the known biological roles.
Free and open to the university community and the public.
Zemer Gitai, Department of Molecular Biology