NATure of actin amino-terminal acetylation

Actins constitute a highly structurally conserved family of proteins found in virtually all eukaryotic cells, in which they participate in processes such as production of contractile force, structural stabilization of the cell, cell motility, endocytosis, and exocytosis (1). The actin monomer, or G-actin, has a nucleotide-binding cleft separating two large domains. Each of these is separated into two subdomains, with the N terminus appearing as an arm which originates from subdomain 1 (Fig. 1). In the context of the actin filament (F-actin), a two-stranded helix, subdomain 1 is located on the filament exterior. This position allows the N-terminal region to be a site of interaction for myosin and a number of other actin-binding regulatory proteins (2, 3). Actins are characterized by an acidic N-terminal region consisting of two to four acidic amino acids in which the N-terminal amino acid is N-acetylated. However, in mature actins, the initiator methionine is missing. In the early 1980s, a series of papers reported the discovery of a unique processing pathway leading to the production of the pure actin (4⇓–6). For class I actins, in which the initiator methionine directly precedes the eventual N-terminal acid residue, the methionine is acetylated. Then the acetyl-methionine is removed proteolytically, exposing the N-terminal acidic amino acid, which is then acetylated to produce the mature form of the protein. Examples of these actins are the beta and gamma cytoplasmic actins found in mammalian cells. For class II actins, which include the striated and smooth muscle actins in mammalian cells, the N-terminal processing is more complex. These proteins are produced from genes which encode a Met-Cys-acidic residue N terminus. For these actins, following removal of the initiator acetyl-methionine, the new N-terminal cysteine is N-acetylated. The acetyl-cysteine is then removed proteolytically to expose the eventual N-terminal acidic residue, … [↵][1]1To whom correspondence should be addressed. Email: peter-rubenstein{at}uiowa.edu. [1]: #xref-corresp-1-1