Structural characterization of rod phosphodiesterase 6 using mass spectrometry

University Of New Hampshire, Durham NH

Investigators

Abstract

With this award, the Chemistry of Life Processes Program is supporting the collaborative research of Drs. Feixia Chu and Rick Cote at University of New Hampshire on the structural characterization of a central phototransduction effector enzyme, photoreceptor phosphodiesterase-6 (PDE6). PDE6 modulates cGMP levels in the photoreceptor outer segment to define the amplitude, duration and adaptation of the photoresponse in vertebrate photoreceptors. This study aims to elucidate the structural determinants of PDE6 allosteric regulators, the spatial organization and molecular recognition of the dynamic PDE6 signaling complex. This research is interdisciplinary, involving the combination of mass spectometry and protein biochemistry to study the underlying structural elements that govern the PDE6 activation/deactivation cycle. This work is expected to both shed light on key events in the visual cycle and the molecular level, focusing on a key protein involved in signal transduction. In a more general sense, the work is expected to lead to strategies and methods to detect protein conformational change, especially in structurally heterogeneous systems, with potentially applicability to technically challenging membrane proteins and protein complexes. The interdisciplinary nature of this project will expose undergraduate and graduate students and a postdoctoral trainee to a broad set of skills at the interface of biochemistry, mass spectrometry-based proteomics and structural analysis. In addition to the proposed research, the research team personnel will continue to participate in education and outreach efforts at the Chemistry/Biology interface at the University of New Hampshire.