Molecular mechanisms for multitasking: recent crystal structures of moonlighting proteins

Recently determined X-ray crystal structures of moonlighting proteins are helping to elucidate how a protein can evolve two different functions and, in some cases, switch between its two functions in response to cellular conditions. X-ray crystal structures of the I-Anil homing endonuclease/maturase and the PutA proline dehydrogenase/transcription factor have provided evidence that these proteins utilize separate protein surfaces for their multiple functions. Also, the structure of the DegP (HtrA) protease/chaperone has revealed information about the mechanism of its chaperone activity and suggests how the protein regulates its protease activity. Comparing the structure of eta-crystallin/retinal dehydrogenase with structures of its single-function enzyme homologs provides clues to changes in the protein structure that may have improved its ability to serve as a crystallin, but at the same time may have adversely affected its catalytic activity.