John Spudich, Ph.D.
Professor and Robert A. Welch Distinguished Chair in Chemistry; Director, Center for Membrane Biology; Fellow, American Academy of Arts & Sciences


Description of Research

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.

Demonstrated Functions of Microbial Rhodopsins in Nature.  BR,  bacteriorhodopsins;  HR,  halorhodopsins;  NaR,  sodium ion pumping rhodopsin;  SRI & SRII,  sensory rhodopsins I & II;  ASR,  Anabaena sensory rhodopsin;  CCRs,  cation-conducting channelrhodopsins;  ACRs,  anion-conducting channelrhodopsins;  SR enzymes,  sensory rhodopsin enzymes.  Demonstrated functions are illustrated in green.  (?) denotes that the indicated functions of ASR and ACRs are suggested but have not been proven.  One SR enzyme, a guanylyl cyclase, has been shown to mediate phototaxis in the flagellated swimming zoospores of a fungus;  other SR enzymes are of unknown physiological function.

Demonstrated Functions of Microbial Rhodopsins in Nature. BR, bacteriorhodopsins; HR, halorhodopsins; NaR, sodium ion pumping rhodopsin; SRI & SRII, sensory rhodopsins I & II; ASR, Anabaena sensory rhodopsin; CCRs, cation-conducting channelrhodopsins; ACRs, anion-conducting channelrhodopsins; SR enzymes, sensory rhodopsin enzymes. Demonstrated functions are illustrated in green. (?) denotes that the indicated functions of ASR and ACRs are suggested but have not been proven. One SR enzyme, a guanylyl cyclase, has been shown to mediate phototaxis in the flagellated swimming zoospores of a fungus; other SR enzymes are of unknown physiological function.

Contact Information

John.L.Spudich@uth.tmc.edu

UTHealth Medical School
Department of Biochemistry and Molecular Biology
Center for Membrane Biology
6431 Fannin Street, MSB 6.200
Houston, Texas 77030

713-500-5473 Direct  713-500-0652 Fax

Education

Ph.D. - University of California, Berkeley

Jane Coffin Childs Postdoctoral Fellow - Harvard Medical School

Research Interests

Light sensors & photosensory transduction, Microbial rhodopsins, Membrane receptor structure/function, Optogenetics

Publications

Characterization of a highly efficient blue-shifted channelrhodopsin from the marine alga Platymonas subcordiformis.

Govorunova EG, Sineshchekov OA, Li H, Janz R, Spudich JL.

J Biol Chem. 2013 Oct 11;288(41):29911-22. doi: 10.1074/jbc.M113.505495. Epub 2013 Aug 30.

PMCID:  PMC3795289

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Cross-protomer interaction with the photoactive site in oligomeric proteorhodopsin complexes.

Ran T, Ozorowski G, Gao Y, Sineshchekov OA, Wang W, Spudich JL, Luecke H.

Acta Crystallogr D Biol Crystallogr. 2013 Oct;69(Pt 10):1965-80. doi: 10.1107/S0907444913017575. Epub 2013 Sep 20.

PMID: 24100316

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Natural light-gated anion channels: A family of microbial rhodopsins for advanced optogenetics.

Govorunova EG, Sineshchekov OA, Janz R, Liu X, Spudich JL.

Science. 2015 Jun 25. pii: aaa7484. [Epub in Science Express ahead of print]

PMID: 26113638

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