View Annual Report - Jules Stein Eye Institute

Wayne L. hubbell, PhD
Jules Stein Professor of Ophthalmology
Distinguished Professor of Chemistry and Biochemistry
Co-Chief of the Vision Science Division
Associate Director of the Jules Stein Eye Institute
ReseaRch summaRy
Molecular Basis of Phototransduction
in the Vertebrate Retina
Dr. Hubbell’s research is focused on understanding the
complex relationship between molecular structure,
plasticity, and conformational changes that control
protein function in the visual system. Of particular
interest are proteins that behave as “molecular switches,”
that is proteins whose structures are switched to an
active state by a physical or chemical signal. Examples
include rhodopsin, the membrane-bound photoreceptor
protein of the retina, and transducin and arrestin, pro-
teins that associate with rhodopsin during function.
The overall goal is to determine the structure of these
proteins in their native environment, monitor the changes
in structure that accompany the transition to an active
state, and to understand the role of protein flexibility
in function.
To investigate these and other proteins, Dr. Hubbell’s
laboratory has developed the technique of site-directed
spin labeling, a novel and powerful approach to the
exploration of protein structure and dynamics. By
changing the genetic code, a specific attachment point
in the protein is created for a nitroxide spin label probe.
Analysis of the electron paramagnetic resonance (EPR)
spectrum of the spin label provides information about
the local environment in the protein. With a sufficiently
large set of labeled proteins, global information on
structure is obtained and changes in the structure
during function can be followed in real time. While
determination of static protein structure is important
to understanding function, current research has highlighted
a crucial role for protein flexibility (dynamics),
which has not been previously appreciated. To explore
molecular flexibility in proteins of the visual system,
Dr. Hubbell’s group is developing novel methods using
time-domain and high-pressure EPR.
46 Faculty | Hubbell
Public Service
Member, National Academy of Sciences
Member, American Academy of Arts and Sciences
Honors
Elected as a Fellow of the International Society of
Magnetic Resonance in Medicine
Research Grants
National Eye Institute: Molecular Basis of
Membrane Excitation, 5/1/05–4/30/13
National Eye Institute: Core Grant for Vision Research
at the Jules Stein Eye Institute (received an ARRA
Administrative Supplement), 3/1/10–2/28/15