John Spudich, PhD
- Director, Center for Membrane Biology
- Robert A. Welch Distinguished Chair in Chemistry
- University of California, Berkeley
- Jane Coffin Childs Postdoctoral Fellow
- Harvard Medical School
Areas of Interests
Light sensors and photosensory transduction, Microbial rhodopsins, Membrane receptor structure/function, Optogenetics
Structure and function of microbial and animal rhodopsins
The primary interests in our laboratory are the mechanisms by which photosensory receptors sense and transmit information concerning the color, intensity, and pattern of light in the environment. We study a widespread class of photoactive receptor proteins (rhodopsins) that consist of seven transmembrane helices connected by interhelical loops. The helices form a pocket for the photosensitive molecule vitamin-A aldehyde (retinal) that attaches in a covalent linkage to a lysine residue in the middle of the 7th helix buried in the core of the protein. These proteins are used for visual processes of various degrees of sophistication, ranging from detection of light-dark boundaries, light gradients, and light direction by single-cell microorganisms to high-resolution color image detection by higher animal eyes.
Photoisomerization of the retinylidene chromophore initiates a variety of types of signaling reactions. Mammalian visual pigments signal by binding and activating heterotrimeric G-proteins. Four distinctly different modes of signaling have been demonstrated for microbial rhodopsins: conformational coupling to bound membrane transducer subunits that relay signals to sensory pathways in the cytoplasm, binding to a cytoplasmic transducer, light-gated ion channel conduction, and light-regulated enzymatic activity encoded by the sensory rhodopsin protein. In addition, homologous microbial rhodopsins pumps drive active ion transport. Our laboratory studies in terms of structure/function how evolution has produced these distinctly different molecular functions from a shared protein scaffold.