NatA

NatA is a major protein N-terminal acetyltransferase complex in eukaryotes that catalyzes the N-terminal acetylation of nascent polypeptides as they emerge from the ribosome. In humans, the core complex comprises the catalytic subunit NAA10 and the auxiliary subunit NAA15; in other organisms, such as yeast, the equivalent complex is known as Ard1–Nat1. NatA associates with ribosomes and acts co-translationally to modify a large portion of newly synthesized proteins.

The activity of NatA depends on the initiator methionine being removed from many substrates. After methionine aminopeptidase cleavage, NatA preferentially acetylates N-termini that begin with small, uncharged residues, including Ser, Ala, Thr, Val, Gly, and Cys. This specificity distinguishes NatA from other N-terminal acetyltransferases that target different N-terminal sequences. NatA’s substrate range contributes to broad effects on protein function and fate.

NatA function is regulated through interactions with other proteins. The NatA complex can associate with chaperone-like factors such as HYPK, which can modulate activity, and it may interact with additional subunits or factors in various organisms to influence substrate scope and efficiency. In some contexts, auxiliary enzymes can extend or alter the acetylation pattern of NatA substrates.

Biological significance and disease associations include effects on protein stability, localization, and interactions, with implications for development and signaling pathways. Mutations in NAA10 or NAA15 have been linked to developmental disorders; notably, certain NAA10 variants cause Ogden syndrome, a severe X-linked condition. NatA’s activity and regulation are active areas of research due to their widespread influence on the proteome.