Please use this identifier to cite or link to this item: https://doi.org/10.1128/MCB.01719-08
Title: Topology of mammalian isoprenylcysteine carboxyl methyltransferase determined in live cells with a fluorescent probe
Authors: Wright, L.P
Court, H
Mor, A
Ahearn, I.M
Casey, P.J 
Philips, M.R
Keywords: amino acid
cyan fluorescent protein
protein s isoprenylcysteine o methyltransferase
asparagine
fluorescent dye
mutant protein
proline
protein methyltransferase
protein s isoprenylcysteine o methyltransferase
protein-S-isoprenylcysteine O-methyltransferase
animal cell
article
controlled study
cytoplasm
cytosol
embryo
endoplasmic reticulum
enzyme activity
enzyme localization
human
human cell
nonhuman
priority journal
protein structure
amino acid substitution
animal
cell strain COS1
cell survival
Cercopithecus
chemistry
enzymology
glycosylation
kinetics
metabolism
nucleotide sequence
protein secondary structure
protein tertiary structure
Mammalia
Saccharomyces cerevisiae
Amino Acid Substitution
Animals
Asparagine
Cell Survival
Cercopithecus aethiops
Conserved Sequence
COS Cells
Cytosol
Endoplasmic Reticulum
Fluorescent Dyes
Glycosylation
Humans
Kinetics
Mutant Proteins
Proline
Protein Methyltransferases
Protein Structure, Secondary
Protein Structure, Tertiary
Issue Date: 2009
Citation: Wright, L.P, Court, H, Mor, A, Ahearn, I.M, Casey, P.J, Philips, M.R (2009). Topology of mammalian isoprenylcysteine carboxyl methyltransferase determined in live cells with a fluorescent probe. Molecular and Cellular Biology 29 (7) : 1826-1833. ScholarBank@NUS Repository. https://doi.org/10.1128/MCB.01719-08
Rights: Attribution 4.0 International
Abstract: Isoprenylcysteine carboxyl methyltransferase (Icmt) is a highly conserved enzyme that methyl esterifies the a carboxyl group of prenylated proteins including Ras and related GTPases. Methyl esterification neutralizes the negative charge of the prenylcysteine and thereby increases membrane affinity. Icmt is an integral membrane protein restricted to the endoplasmic reticulum (ER). The Saccharomyces cerevisiae ortholog, Ste14p, traverses the ER membrane six times. We used a novel fluorescent reporter to map the topology of human Icmt in living cells. Our results indicate that Icmt traverses the ER membrane eight times, with both N and C termini disposed toward the cytosol and with a helix-turn-helix structure comprising transmembrane (TM) segments 7 and 8. Several conserved amino acids that map to cytoplasmic portions of the enzyme are critical for full enzymatic activity. Mammalian Icmt has an N-terminal extension consisting of two TM segments not found in Ste14p and therefore likely to be regulatory. Icmt is a target for anticancer drug discovery, and these data may facilitate efforts to develop small-molecule inhibitors. Copyright © 2009, American Society for Microbiology.
Source Title: Molecular and Cellular Biology
URI: https://scholarbank.nus.edu.sg/handle/10635/181012
ISSN: 02707306
DOI: 10.1128/MCB.01719-08
Rights: Attribution 4.0 International
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1128_MCB_01719-08.pdf2.11 MBAdobe PDF

OPEN

NoneView/Download

Google ScholarTM

Check

Altmetric


This item is licensed under a Creative Commons License Creative Commons