A novel human NatA Nalpha-terminal acetyltransferase complex: hNaa16p-hNaa10p (hNat2-hArd1).
BACKGROUND
Protein acetylation is among the most common protein modifications. The two major types are post-translational Nepsilon-lysine acetylation catalyzed by KATs (Lysine acetyltransferases, previously named HATs (histone acetyltransferases) and co-translational Nalpha-terminal acetylation catalyzed by NATs (N-terminal acetyltransferases). The major NAT complex in yeast, NatA, is composed of the catalytic subunit Naa10p (N alpha acetyltransferase 10 protein) (Ard1p) and the auxiliary subunit Naa15p (Nat1p). The NatA complex potentially acetylates Ser-, Ala-, Thr-, Gly-, Val- and Cys- N-termini after Met-cleavage. In humans, the homologues hNaa15p (hNat1) and hNaa10p (hArd1) were demonstrated to form a stable ribosome associated NAT complex acetylating NatA type N-termini in vitro and in vivo.


RESULTS
We here describe a novel human protein, hNaa16p (hNat2), with 70% sequence identity to hNaa15p (hNat1). The gene encoding hNaa16p originates from an early vertebrate duplication event from the common ancestor of hNAA15 and hNAA16. Immunoprecipitation coupled to mass spectrometry identified both endogenous hNaa15p and hNaa16p as distinct interaction partners of hNaa10p in HEK293 cells, thus demonstrating the presence of both hNaa15p-hNaa10p and hNaa16p-hNaa10p complexes. The hNaa16p-hNaa10p complex acetylates NatA type N-termini in vitro. hNaa16p is ribosome associated, supporting its potential role in cotranslational Nalpha-terminal acetylation. hNAA16 is expressed in a variety of human cell lines, but is generally less abundant as compared to hNAA15. Specific knockdown of hNAA16 induces cell death, suggesting an essential role for hNaa16p in human cells.


CONCLUSIONS
At least two distinct NatA protein Nalpha-terminal acetyltransferases coexist in human cells potentially creating a more complex and flexible system for Nalpha-terminal acetylation as compared to lower eukaryotes.
Arnesen
Thomas
T
Department of Molecular Biology, University of Bergen, N-5020 Bergen, Norway. Thomas.Arnesen@mbi.uib.no
Gromyko
Darina
D
Kagabo
Diane
D
Betts
Matthew J
MJ
Starheim
Kristian K
KK
Varhaug
Jan Erik
JE
Anderson
Dave
D
Lillehaug
Johan R
JR
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000595:Amino Acid Sequence; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism / Q000502:physiology*; D016923:Cell Death; D045744:Cell Line, Tumor; D019143:Evolution, Molecular; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000502:physiology*; D063213:N-Terminal Acetyltransferase E; D063206:N-Terminal Acetyltransferases; D010455:Peptides / Q000378:metabolism; D010802:Phylogeny; D011499:Protein Processing, Post-Translational; D012270:Ribosomes / Q000378:metabolism; D016415:Sequence Alignment
D007527:Isoenzymes; D009097:Multienzyme Complexes; D010455:Peptides; D000123:Acetyltransferases; D063213:N-Terminal Acetyltransferase E; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1; C478900:NAT2 protein, human; D063206:N-Terminal Acetyltransferases; C522989:NAT10 protein, human