Tom H. Stevens

Scholar: 1984

Awarded Institution
Professor of Chemistry and Director
University of Oregon
Institute of Molecular Biology


Research Interests

Tom Stevens's research group is concerned with the process of protein sorting and organelle assembly in yeast cells as well as in a newly discovered process termed protein splicing. Yeast molecular genetics has allowed the researchers to identify a large number of genes required for the correct targeting and transport of proteins to the organelle called the vacuole, and these vacuolar protein sorting (VPS) genes have been found to encode proteins such as a dynamin like GTPase, a protein sorting receptor, a protein kinase, a lipid kinase, a RAS inhibitor like protein, and an increasingly large number of proteins involved in vesicle transport such as Rab like GTPases, Secl like and syntaxin like proteins. To characterize the function of some of these proteins the group has developed an in vitro assay that reconstitutes the Golgi to vacuole transport step. Standard biochemical approaches are being used to isolate these VPS proteins and to study the membrane associated protein complexes to which they belong.

Investigations into the mechanism of targeting integral membrane proteins in yeast has led to the discovery of a short peptide stretch rich in aromatic amino acids that functions to retain membrane proteins within the Golgi compartment. This work has now led to the isolation of several yeast genes involved in the process of Golgi membrane protein retention. Among the genes identified, one is likely to encode a receptor that binds to the aromatic amino acid rich Golgi retention signal.

The group also has a long standing interest in the assembly, targeting, and function of the vacuolar H+-translocating ATPase (V-ATPase). Having cloned and characterized most of the subunit encoding genes, the group has now turned its focus to understanding how this protein is assembled and targeted to the vacuole. Several genes have been characterized that encode proteins required for V-ATPase complex assembly but are not part of the final enzyme. The group is currently characterizing a complex of proteins that functions in the V-ATPase assembly process.

The group has recently discovered a new biological process termed protein splicing. Protein splicing refers to the removal of a section out of the middle of a protein and the subsequent reformation of a peptide bond to form the mature processed protein. To date there are three examples in nature of proteins undergoing this extraordinary post translational process. The evidence indicates that the reaction proceeds by a unimolecular reaction and is thus analogous to self splicing introns. The detailed mechanism of this intriguing reaction is under investigation in this laboratory.