Ntermini

N-termini are the amino termini of proteins or peptides, representing the starting end of a polypeptide chain. In translation, proteins typically begin with an initiator methionine, which is often removed by methionine aminopeptidase, leaving an N-terminus defined by the second residue. Some proteins retain the initiator methionine, producing a different N-terminus.

N-termini can be shaped by processing events that produce mature termini different from the gene-encoded sequence. N-terminal signal peptides direct polypeptides to the secretory pathway and are usually removed after targeting. Mitochondrial and chloroplast transit sequences, also at the N-terminus, are cleaved upon import, generating a mature protein with a new N-terminal residue.

Modifications at the N-terminus are common and can influence protein behavior. N-terminal acetylation, carried out by N-terminal acetyltransferases, is widespread in eukaryotes and can affect stability, localization, and interactions. In some cases, a newly exposed N-terminal glycine after initiator methionine removal can undergo N-myristoylation, a lipid modification that can affect membrane association.

The N-end rule pathway links the identity of the N-terminal residue to protein stability. Certain N-terminal residues act as stabilizing elements, while others function as degrons that target proteins for rapid degradation. This relationship informs predictions about protein half-life and turnover.

N-terminomics is a field focused on identifying and characterizing protein N-termini and N-terminal processing. Techniques include specialized mass spectrometry approaches and proteolytic labeling methods to map start sites, cleavage events, and modification states across proteomes. Understanding N-termini aids in annotating translation starts, maturation processes, localization, and stability, with implications for biology and disease.