Research Interests
Interactions of biomolecules with light forms is a unifying theme for research in my group. Step-scan time-resolved FTIR spectra are used to examine dynamics of protein conformational changes, using a variety of biochemical modifications to aid in accounting for the observed spectra. We have also developed 20-micron-thick Ge waveguide biosensors for analyzing the membranes of individual living cells with IR spectroscopy.
We are especially interested in membrane proteins that bind derivatives of vitamin A, resulting in a photochemical response to visible or UV light. The majority of our recent effort has been on proteorhodopsin (pR), a solar-energy-transducing protein discovered in oceanic bacteria only in the year 2000. Proteorhodopsin is a distant relative of archaeal membrane proteins that have been known for several decades to pump protons from the cytoplasm to the exterior of the cell. Solar energy transduction by pR throughout the oceans is estimated to approach or exceed total worldwide human energy consumption (∼10 trillion watts). Our recent work has shown that the mechanism of proton pumping in the protein superfamily depends on a transient decrease in the proton affinity of a highly conserved arginine residue, leading to its transient deprotonation, with proton release to the external side of the membrane.
 We can model the proton releasing group of the microbial rhodopsins with a simple but novel synthetic molecule, consisting of an arginine side chain (guanidine) attached to a tyrosine side chain (phenol) via a long alkane linker. We are also investigating this class of compounds for possible pharmacological properties, since the arginine-tyrosine grouping is also highly conserved and mechanistically important to the visual rhodopsins and entire related superfamily of G-protein-coupled receptors.
We are examining the role of retinoic acid, another vitamin A derivative, in mediating the skin's response to ultraviolet light. Up to one-sixth of a person's retinoic acid is converted to the 11-cis form in an hour of exposure to midday sun. This isomer has the greatest ability to halt the growth of keratinocytes in cell culture. Thus 11-cis-retinoic acid might prevent some of the ill effects of sunlight on skin, e.g. by inducing cells to undergo terminal differentiation. We hope to find some therapeutic uses, possibly even an anti-cancer activity, for this only slightly investigated derivative of vitamin A.
Ultrathin (<10 micron) planar IR waveguide sensors made of germanium provide the means for extending time-resolved IR spectroscopy of membrane proteins to those triggered by voltage changes, rather than light. Such sensors concentrate and amplify the intensity of the IR energy present in the evanescent wave present within ∼1 micron of the germanium surface, allowing measurement of IR spectra from single cells, e.g. frog oocytes.
Selected Publications
M.S. Braiman and Y. Xiao. "Step-scan time-resolved FTIR spectroscopy of biopolymers," in Vibrational Spectroscopy of Biological and Polymeric Materials, eds. V. Gregoriou and M.S. Braiman, CRC Press, Taylor and Francis group (ISBN 1-57444-539-1), pp. 353-418.
Y. Xiao and M. S. Braiman. Modeling amino acid side chains in proteins: 15N NMR spectra of guanidino groups in nonpolar environments. J. Phys. Chem. B, 109:16953-16958. (2005). DOI: 10.1021/jp051279e
R. Partha, R. Krebs, T. L. Caterino, and M. S. Braiman. Weakened coupling of conserved arginine to the proteorhodopsin chromophore and its counterion implies structural differences from bacteriorhodopsin. BBA Bioenergetics, 1708, 6-12. (2005). DOI: 10.1016/j.bbabio.2004.12.009
Y. Xiao, M. S. Hutson, M. Belenky, J. Herzfeld, and M. S. Braiman. Role of Arginine-82 in Fast Proton Release during the Bacteriorhodopsin Photocycle: A Time-Resolved FT-IR Study of Purple Membranes Containing 15N-Labeled Arginine. Biochemistry 43: 12809-12818 (2004). DOI: 10.1021/bi049238g
Vongsvivut, J.; Fernandez, J.; Ekgasit, S.; Braiman, M. S. Characterization of supported cylinder-planar germanium waveguide sensors with synchrotron infrared radiation. Appl. Spectrosc., 58: 143-151 (2004).
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