title: Cargo sequences are important for Som1p-dependent signal peptide cleavage in yeast mitochondria.
abstract: The inner membrane protease (IMP) has two catalytic subunits, Imp1p and Imp2p, that exhibit nonoverlapping substrate specificity in mitochondria of the yeast Saccharomyces cerevisiae. The IMP also has at least one noncatalytic subunit, Som1p, which is required to cleave signal peptides from a subset of Imp1p substrates. To understand how Som1p mediates Imp1p substrate specificity, we addressed the possibility that Som1p functions as a molecular chaperone, which binds to specific substrates and directs them to the catalytic site. Our results show that cargo sequences attached to the signal peptide are important for Som1p-dependent presequence cleavage; however, no specific cargo sequence is required. Indeed, we show that a substrate normally destined for Imp2p is cleaved in a Som1p-dependent manner when the substrate is directed to Imp1p. These results argue against the notion that Som1p is a molecular chaperone. Instead, we propose that the cargo of some Imp1p substrates can assume a conformation incompatible with presequence cleavage. Som1p could thus act through Imp1p to improve cleavage efficiency early during substrate maturation.
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Vanderbilt University, Nashville, Tennessee 37232-2363, USA.
authors.forename: Haobo
authors.initials: H
authors.lastname: Liang
authors.forename: Wentian
authors.initials: W
authors.lastname: Luo
authors.forename: Neil
authors.initials: N
authors.lastname: Green
authors.forename: Hong
authors.initials: H
authors.lastname: Fang
mesh_terms: D015786:Cytochromes b5 / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D017353:Gene Deletion; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D010447:Peptide Hydrolases; D021382:Protein Sorting Signals / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D021382:Protein Sorting Signals; D012097:Repressor Proteins; C102047:SOM1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015786:Cytochromes b5; D010450:Endopeptidases; D010447:Peptide Hydrolases; C067167:IMP1 protein, S cerevisiae