Invertase signal and mature sequence substitutions that delay intercompartmental transport of active enzyme.
The role of structural signals in intercompartmental transport has been addressed by the isolation of yeast invertase (SUC2) mutations that cause intracellular accumulation of active enzyme. Two mutations that delay transport of core-glycosylated invertase, but not acid phosphatase, have been mapped in the 5' coding region of SUC2. Both mutations reduce specifically the transport of invertase to a compartment, presumably in the Golgi body, where outer chain carbohydrate is added. Subsequent transport to the cell surface is not similarly delayed. One mutation (SUC2-s1) converts an ala codon to val at position -1 in the signal peptide; the other (SUC2-s2) changes a thr to an ile at position +64 in the mature protein. Mutation s1 results in about a 50-fold reduced rate of invertase transport to the Golgi body which is attributable to defective signal peptide cleavage. While peptide cleavage normally occurs at an ala-ser bond, the s1 mutant form is processed slowly at the adjacent ser-met position giving rise to mature invertase with an N-terminal met residue. s2 mutant invertase is transported about sevenfold more slowly than normal, with no delay in signal peptide cleavage, and no detectable abnormal physical property of the enzyme. This substitution may interfere with the interaction of invertase and a receptor that facilitates transport to the Golgi body.
D001692:Biological Transport; D002451:Cell Compartmentation; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D009154:Mutation; D010455:Peptides / Q000502:physiology; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics; D012697:Serine Endopeptidases; D043324:beta-Fructofuranosidase
D006023:Glycoproteins; D008565:Membrane Proteins; D010455:Peptides; D021382:Protein Sorting Signals; D006026:Glycoside Hydrolases; D043324:beta-Fructofuranosidase; D010450:Endopeptidases; D012697:Serine Endopeptidases; C026515:type I signal peptidase