TY - JOUR
T1 - Genetic manipulation indicates that ARD1 is an essential Nα-acetyltransferase in Trypanosoma brucei
AU - Ingram, Alexandra K.
AU - Cross, George A.M.
AU - Horn, David
N1 - Funding Information:
We would like to thank John Kelly, Martin Taylor and Carolina Mailhos for critical reading of the manuscript and Elizabeth Wirtz for helpful discussions during the earlier stages of these studies. This work was supported by The Royal Society (574006), the National Institutes of Health (AI21729) and by a Research Career Development Fellowship to D.H. from The Wellcome Trust (052323).
PY - 2000
Y1 - 2000
N2 - Nα-acetylation, the most common protein modification, involves the transfer of an acetyl group from acetyl-coenzyme A to the N-terminus of a protein or peptide. The major Nα-acetyltransferase in Saccharomyces cerevisiae is the ARD1-NAT1 complex. To investigate Nα-acetylation in Trypanosoma brucei we have cloned and characterised genes encoding putative homologues of ARD1 and NAT1. Both genes are single copy and ARD1, the putative catalytic component, is expressed in both bloodstream-form and insect-stage cells. In either of these life-cycle stages, disruption of both ARD1 alleles was only possible when another copy was generated via gene duplication or when ARD1 was expressed from elsewhere in the genome. These genetic manipulations demonstrate that, unlike the situation in S. cerevisiae, ARD1 is an essential gene in T. brucei. We propose that protein modification by ARD1 is essential for viability in mammalian and insect-stage T. brucei cells.
AB - Nα-acetylation, the most common protein modification, involves the transfer of an acetyl group from acetyl-coenzyme A to the N-terminus of a protein or peptide. The major Nα-acetyltransferase in Saccharomyces cerevisiae is the ARD1-NAT1 complex. To investigate Nα-acetylation in Trypanosoma brucei we have cloned and characterised genes encoding putative homologues of ARD1 and NAT1. Both genes are single copy and ARD1, the putative catalytic component, is expressed in both bloodstream-form and insect-stage cells. In either of these life-cycle stages, disruption of both ARD1 alleles was only possible when another copy was generated via gene duplication or when ARD1 was expressed from elsewhere in the genome. These genetic manipulations demonstrate that, unlike the situation in S. cerevisiae, ARD1 is an essential gene in T. brucei. We propose that protein modification by ARD1 is essential for viability in mammalian and insect-stage T. brucei cells.
KW - Acetylation
KW - Acetyltransferase
KW - Protein modification
KW - Trypanosoma brucei
UR - http://www.scopus.com/inward/record.url?scp=0034494265&partnerID=8YFLogxK
U2 - 10.1016/S0166-6851(00)00322-4
DO - 10.1016/S0166-6851(00)00322-4
M3 - Article
C2 - 11163439
AN - SCOPUS:0034494265
SN - 0166-6851
VL - 111
SP - 309
EP - 317
JO - Molecular and Biochemical Parasitology
JF - Molecular and Biochemical Parasitology
IS - 2
ER -