Signal peptidase
The signal peptidase is an evolutionarily conserved membrane protease that cleaves the N-terminal signal peptide of secretory proteins. While prokaryotic signal peptidases function in a monomer, eukaryotic ones contain two non-catalytic subunits, Spc1 and Spc2.
Recently, we have found that transmembrane segments of membrane proteins become susceptible to cleavage by signal peptidase when Spc1 is deleted. When Spc1 was overexpressed, membrane protein processing was reduced, indicating that it regulates selection of membrane proteins for processing. Currently, we are investigating the roles of Spc1 and Spc2 in signal peptidase and their possible involvement in membrane protein biogenesis and degradation.
Topogenesis of membrane proteins
Topogenesis of membrane proteins refers to the process that transmembrane domains are inserted into the lipid bilayer while soluble domains properly localize and fold in either side of the membrane during their biogenesis. This process requires spatiotemporal coordination of folding of soluble domains with membrane insertion of transmembrane domains.
While the text book view illustrates that flanking charged residues of the first transmembrane domain of the membrane protein dictates its orientation relative to the membrane, accumulating data suggest that membrane insertion and folding of soluble domains are more intricate and complex than currently understood. We investigate the components that mediate these processes and analyze sequence characteristics of polypeptides that contribute in topogenesis of membrane proteins.
Mitochondrial targeting sequences
Mitochondrial targeting sequences (MTS) function in targeting and import of nuclear encoded proteins to the mitochondria. Unlike the ER signal sequences, the length of MTS greatly varies between 15-150. Although it has been thought that mitochondrial proteins are targeted posttranslationally (after complete synthesis of proteins), recent studies show that mitochondrial inner membrane proteins which contain hydrophobic transmembrane domains are cotranslationally targeted, and via the ER membrane. How diverse types of MTS direct proteins to mitochondria and what sequence characteristics in MTS and mature domain region contribute in proper targeting in vivo largely remain unknown, and we aim to answer to these questions.