Moonlighting proteins—an update

Abstract

A growing number of diverse proteins are being identified that moonlight. Moonlighting proteins comprise an interesting subset of multifunctional proteins in which the two functions are found in a single polypeptide chain. They do not include proteins that are multifunctional due to gene fusions, families of homologous proteins, splice variants, or promiscuous enzyme activities. This review summarizes recent discoveries that add to the list of known moonlighting proteins. They include several different kinds of proteins and combinations of functions. In one case, a novel DNA binding function was found for a biosynthetic enzyme through a proteomics microarray project. The review also summarizes recent X-ray crystal structures that provide clues to the molecular mechanisms of one or both functions, and in some cases how a protein can switch between functions. In addition, the possibility that many proteins with intrinsically unstructured regions might also moonlight is discussed.