A Simple Rule for Proteins to Follow

Proteins are the workhorses of cells, acting as enzymes, structural elements, and signal transducers. The tremendous variability in proteins’ chemical and physical properties is achieved through the manner in which they are made—by the mixing and matching of a set of basic building blocks known as amino acids. Each amino acid consists of a carbon atom attached to an amine group, a carboxyl group, a hydrogen atom, and one of 22 structurally and chemically distinct side groups. When a cell builds a protein, it uses the instructions encoded in a corresponding gene to tell it which amino acids to use, and in what order. A new protein is assembled front-to-back, with each new amino acid added to the growing chain by hooking its amine group to the carboxyl group of the previous amino acid. The business of protein assembly is just the first step in creating a functional protein. Once assembled, a protein must next be folded into the proper 3-D shape for its designated cellular function. Then, it may be further altered by a myriad of chemical modifications, which can affect anything from its activity level, to its location within the cell, to its longevity. One such modification, called amino terminal acetylation (N-acetylation), involves adding an acetyl group to the amine group of a protein’s first amino acid. N-acetylation affects around 80%– 90% of proteins in human cells (and about 50% in yeast). Researchers think Nacetylation occurs as a protein is being made, and that, in some cases, it may affect a protein’s proper location, stability, and function within the cell. Until now, the rules governing whether a given protein receives this modification weren’t fully understood, a situation rectified in a paper by Sandra Goetze, Erich Brunner, and colleagues in this issue of PLoS Biology. The enzymes that carry out N-acetylation are known as N-terminal acetyltransferases (NATs). They have been identified in yeast and humans and appear to work by recognizing specific sequences of amino acids. However, it turns out that simply being recognized by NATs does not guarantee that N-acetylation will occur; many proteins containing the appropriate recognition sequences lack N-acetylation. Goetze and colleagues postulated that some other feature of proteins overrides NAT recognition to control whether the protein receives N-acetylation. To explore this possibility, the authors turned to a favorite experimental system— the fruit fly. N-acetylation had been thought to be rare in flies, as few proteins with this modification had so far been identified in invertebrates. But, when Goetze and colleagues looked for Nacetylation on proteins purified from Drosophila Kc167 cells, they found that