Photoinduced localized unfolding of tubulin heterodimers mediated by a water soluble porphyrin: structural and functional studies

Date
2015
Authors
McMicken, Brady
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Abstract

The ability to modify the conformation of a protein by controlling its partial unfolding may have practical applications such as inhibiting a particular function of a protein. One novel method of locally unfolding a protein involves the use of a light-activated ligand or photosensitizer which is non-covalently bound to a protein. The irradiation of the ligand triggers photochemical reactions that prompt conformational changes in the protein. We investigate the effects of irradiating the bound complex formed by a water soluble porphyrin and the protein tubulin in an attempt to induce a conformation change of the protein through the photophysics of the porphyrin. It is also instructive to study the effects that the unfolding of tubulin may have on its function of forming microtubules and the mechanism responsible for the structural change (i.e. electron transfer or production of reactive oxygen species). Density functional theory calculations can be combined with Resonance Raman spectroscopy to correlate the changes in vibrational modes of the porphyrin with changes in its geometry upon binding to tubulin. This will allow us to determine the distorted conformation of the porphyrin bound to tubulin which will subsequently be used in docking simulations to find the most likely binding configuration. Lastly, we investigate whether two photon excitation of the porphyrin can also trigger conformational changes in the protein. A two-photon event would give the method better spatial resolution in some cases and allow irradiation to have deeper material penetration.

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Keywords
atomic force microscopy, docking, Microtubules, porphyrin, Raman, two-photon absorption
Citation
Department
Physics and Astronomy