Colloquium 2008-02-21

 

3:30 p.m. in Room 307 of the Optical Sciences Meinel Building

Speaker:

Michael Cusanovich

 

Title:

PAS Domain Containing Light-Activated Switches

 

Host:

Stanley Pau

 

Abstract:

Photoactive yellow protein (PYP), a small (~15,000 mol. wt.) water soluble blue light sensor, is a member of a superfamily of PAS domain containing sensor proteins, and is the structural prototype for over 5,000 known PAS domain containing sensor proteins found throughout the evolutionary tree. PYP is a blue light sensor, however, the PAS superfamily is not restricted to light sensing, and depending on species functions can range from oxygen, electric field and redox sensing to small molecule sensing (for example, a wide range of small organic molecules and metabolites). The functional diversity of PAS domains is an outstanding example of the use of a common structural motif, which adapted through evolution to address the specific metabolic needs of a specific organism. PYP undergoes a photoisomerization (trans  p-hydroxy cinnamic acid to cis) in ~3 ps, that initiates a series of structural changes (photocycle) leading to the lit or signaling state, which then activates a response regulator leading to function. The lit state spontaneously reverts to the dark state to complete the photocyclye. The formation of the lit state is coupled with a major conformational change. Many of the PAS domain containing sensor proteins are complex consisting of two or more interacting domains.

 

A major focus of our work is on a blue-red light sensing protein, called Ppr, which contains PYP, bacteriophytochrome and histidine kinase domain, that phosphorylates a transcriptional regulator when activated, which turns on the expression of a polyketide synthase. Our goal is to characterize the transient structural changes leading to the lit state, and the mechanism by which the PYP, Bph and histidine kinase interact leading to the light activation of the kinase.

 

Photoactive Yellow Protein: A Prototypic PAS Domain Sensory Protein and Development of a Common Mechanism for the Two-Component Regulatory Family. M. A. Cusanovich and T. E. Meyer, Biochem. 42, 4759-70 (2003).

 

The Photoactivated PYP Domain of Rhodospirillum centenum  Ppr Accelerates Recovery of  the Bacteriophytochrome Domain After White Light Illumination.‘  John A. Kyndt, John C. Fitch, Terry E. Meyer, and Michael A. Cusanovich,  Biochem 46, 8256-62 (2007).