Scientists Decode How Cells Add Fatty Acids to Proteins During Translation

This groundbreaking study solves a long-standing puzzle in cell biology: how cells precisely attach fatty acids to newly made proteins. N-myristoylation—the addition of myristic acid to protein N-termini—affects over 500 human proteins and is essential for their proper function and cellular localization.

Using advanced cryo-electron microscopy and biochemical techniques, researchers mapped exactly how the enzyme NMT1 interacts with ribosomes during protein synthesis. They discovered that NMT1 works in concert with the nascent polypeptide-associated complex (NAC) and exchanges positions with methionine aminopeptidase (METAP1) at the ribosome's exit tunnel in a carefully choreographed sequence.

The key finding is that NMT1 binding is sequence-selective and specifically triggered when METAP1 removes the initial methionine residue, exposing the glycine that becomes the target for myristoylation. This timing mechanism ensures that only appropriate proteins receive the fatty acid modification while preventing competing enzymes from interfering.

These insights have significant therapeutic implications. NMT enzymes are proven drug targets for cancer and viral infections, with several compounds currently in clinical trials. Understanding the precise molecular mechanism could enable development of more specific inhibitors with fewer side effects. The research also reveals why certain genetic mutations affecting NAC or NMT function lead to disease, providing new avenues for therapeutic intervention.