Structure and Function of Prokaryotic Transcription Factors

University Of California-Irvine, Irvine CA

Investigators

Abstract

The goal of this research is to better understand structure-function relationships in CooA, a carbon monoxide sensing transcription factor. CooA belongs to the classic helix-turn-helix family of bacterial transcription factors. Transcription factors are proteins that bind to select segments of DNA and regulate the transcription of specific genes that encode specific enzymes. This class of transcription factor are homo-dimers with each monomer consisting of an effector domain that binds small regulatory molecules and a DNA-binding domain that recognizes specific DNA sequences. When the regulatory molecule binds to the effector domain, structural changes occur which enables the protein to bind to DNA regulatory sequences. The bound transcription factor next binds RNA polymerase leading to the transcription of specific genes. With CooA, carbon monoxide is the small molecule effector. Carbon monoxide binds to the heme in each effector domain which promotes DNA binding thus leading to the production of enzymes that oxidize CO as an energy source. Previous research lead to the solution of the CooA crystal structure in the DNA "off" state. What now is needed is the crystal structure of CooA in the DNA-bound form which is the focus of this research. If successful, CooA would be the first transcription factor in this family where the structure of both the DNA-bound and -free forms are known. This will provide critical new information on how an effector molecule can cause such large changes in the DNA-binding region of the molecule.