NatB

NatB, short for N-terminal acetyltransferase B, is a protein complex that catalyzes the N-terminal acetylation of a subset of nascent polypeptides in eukaryotic cells. This modification occurs co-translationally, often while the polypeptide is emerging from the ribosome, and can influence protein stability, localization, interactions, and turnover.

The NatB complex is typically composed of two subunits. In humans, the catalytic subunit is NAA20 and the regulatory subunit is NAA25; in the budding yeast Saccharomyces cerevisiae, the corresponding components are Nat3 (catalytic) and Mdm20 (regulatory). The two-subunit assembly defines NatB’s substrate specificity and helps recruit the complex to ribosomes.

NatB targets proteins whose N-terminal sequence arises after initiation methionine removal, commonly exposing acidic or amide-containing residues such as aspartate, glutamate, asparagine, or glutamine. The exact substrate range can vary among species, but the general rule is that NatB acetylates N-termini that begin with Met-X, where X is one of these residues, following methionine excision.

Mechanistically, NatB belongs to the GNAT (GCN5-related N-acetyltransferase) superfamily and uses acetyl-CoA as the acetyl donor to transfer the acetyl group to the α-amino group of the protein’s N-terminus. The regulatory subunit aids in substrate recognition and, in many organisms, in coupling the activity to ribosome association.

Biological significance is attributed to the broad influence of N-terminal acetylation on protein fate and function. Disruption of NatB components can alter the cellular N-terminal acetylation landscape and affect diverse biological processes; NatB is one of several conserved NAT complexes that coordinate post-translational modification of proteins.