Published: Mechanochemistry of Transcription Termination Factor Rho

jadelman — Fri, 09 Jun 2006 20:15:05 +0000

Adelman, J.L, et al. (2006) Molecular Cell 22(5):611-621 :: Rho is a ring-shaped hexameric motor protein that translocates along nascent mRNA transcript and terminates transcription of select genes in bacteria. Using a numerical optimization algorithm that simultaneously fits all of the presteady-state ATPase kinetic data, we determine how Rho utilizes the chemical energy of ATP hydrolysis to translocate RNA. A random hydrolysis mechanism is ruled out by the observed inhibition of ATPase in a mixed hexamer containing wt and an inactive Rho mutant. We propose a mechanism in which (1) all six subunits are catalytically competent and hydrolyze ATP sequentially, (2) translocation of RNA is driven by the weak to tight binding transition of nucleotide in the catalytic site, (3) hydrolysis is coordinated between adjacent subunits by the transmission of stress via the catalytic arginine finger, (4) hydrolysis weakens the affinity of a subunit for RNA, and (5) the slow release of inorganic phosphate is controlled by changes in circumferential stress around the ring.

Poster: Mechanochemical Modeling of DNA Translocases

jadelman — Thu, 22 Jun 2006 05:24:50 +0000

I am funded by the DOE’s Computational Science Graduate Fellowship and one of the great perks of the program is the annual Fellows’ Conference , held in Washington, DC which allows this rather eclectic group to present their research in a highly interdisciplinary setting. This year I presented my preliminary work on modeling DNA Translocases which is a collaborative project with Andrew Spakowitz and members of the Bustamante Lab. Investigating the mechanochemistry of motor proteins by developing simple coarse-grained models is an ongoing theme in my research. This work extends the pure kinetic modeling used in my previous work to couple the conformational dynamics of the protein to the chemical cycle of individual subunits in order to elucidate the effects of external force on the protein’s behavior.

How Rho Exerts Its Muscle on RNA :: Molecular Cell Preview

jadelman — Sun, 25 Jun 2006 03:17:11 +0000

The June 23rd issue of Molecular Cell contains a ‘preview’ by John Richardson of the Mechanochemistry of Transcription Termination Factor Rho, highlighting our experimental and modeling efforts.