A Reciox-Controlieci Molecular Switch Revealed by the Crystal Structure of a Bacterial Heme PAS Sensor·Insights into Signal Transciuctlon involving PAS Domain Oxygen-Sensing Heine Proteins From the X-ray Crystal Structure of Escherichia coll Dos Hem

摘要

PAS domains in proteins function as both signaling and sensing elements. These domains sense changes in light, redox potential, oxygen, and other small ligands, and initiate a signal cascade in response to those changes.1 Many of the sensing PAS domain proteins require a cofactor, such as a coordinated heme, to detect environmental changes.1 PAS domains are contained in a wide variety of proteins with various functions and occur in all three kingdoms of life. They are generally -130 amino acids long and fold into a characteristic three-dimensional structure.1' 2 A prototypical structure of a PAS domain can be seen in the crystal structure of PYP, a photoreceptor from Ectothiorhodospira halophila} PYP exhibits an a/(3 fold with a six-stranded P-sheet, an N-terminal cap, and a-helices in the PAS core and helical connector, Fa, that coordinates the heme.3 Proteins containing PAS domains have a variety of additional functions, such as transcription regulation and maintaining circadian rhythms in mammals, as well as kinase and phosphodiesterase activity.1 A few members of the PAS domain superfamily have been well studied, but little is known about the direct mechanism by which the PAS domain senses the change in environment and propagates the corresponding signal, initiating the appropriate biological response.