Abstract: Do Terahertz Protein Collective Vibrations Contribute to Function?

Conformational change is essential for protein function, however the mechanism governing the efficient access to intermediate state structures remains under debate. Long range structural vibrations have been a candidate facilitating steering towards intermediate conformations, however experimental demonstration of the evolution of the steering before conformational change has not occurred. Biological physics is a discipline where we apply our unique physics training in experimental design and quantitative description to address complex questions in biology.

Our group has worked at the development of spectral measurements of protein structural vibrations. This required identifying the challenges for optical measurements and implementing a strategy to address these. Now that we have data, we can address if and how specific excitations are relevant to biology. Here we discuss measurements of the spectrum and directionality of the protein vibrational bath for the photoprotective protein orange carotenoid protein, which is regulated by blue light intensity, using anisotropic terahertz microspectroscopy. We find that the structural vibrational bands reversibly shift with photoexcitation before large scale conformational change can occur. The results indicate that an early photo intermediate is accompanied with a reorientation of vibrational displacements. Using an ensemble vibrational analysis, we find good agreement with the spectral changes observed with a holo versus apo calculations. Further analysis of the spectral region effected by the illumination shows that the correlated motions corresponding to the observed spectral changes are consistent with local energy changes with small translocations of the chromophores. These energy dynamical changes corresponding to the observed spectral changes are consistent with the required structural reorganization for the photo cycling to proceed. Thus changes in the structural dynamics appear to proceed the large structural change into the photoprotective state.

Bio:

Andrea Markelz is a Professor of Physics at the University at Buffalo, SUNY. Her Bachelor's degree was in Physics and Applied Math from University of California at Berkeley with undergraduate research on oxide superconductors. She did a Masters at Columbia University in Applied Physics and a PhD in Physics at the University of California, Santa Barbara. Her PhD was on the nonlinear optical properties of III-V semiconductor heterostructures at terahertz frequencies. She was awarded an NRC fellowship to initiate a terahertz program at NIST, Gaithersburg. Afterwards she was an NSF GOALI postdoctoral fellow at Bell Labs, Murray Hill, NJ. She began her appointment at University at Buffalo in the Fall of 1999. She has since developed patented terahertz techniques to characterize picosecond dynamics of proteins and polynucleotides. In addition to being a member of various international terahertz organizations, she chaired the 2009 Optical Terahertz Science and Technology conference (OTST 2009), and the 2020 International Conference on Infrared Millimeter and Terahertz Waves (IRMMW 2020). She has more than 100 publications and over 6400 citations. Previous recognitions include an NSF CAREER award in 2004 and a SUNY Exceptional Scholar and Teaching Innovation Award in 2014, and a SUNY Chancellor's Award in Excellence in Research and Creative Activities in 2021.