Event

"Towards Understanding Allostery: Measuring Protein Long Range Vibrations”

Andrea Markelz
Physics Department, University at Buffalo, SUNY

Protein function can often be determined by the binding of an allosteric inhibitor or promoter remote from the catalytic site.  This can occur in the absence of any structural change.  A possible mechanism for this type of allostery is that the binding changes the internal structural dynamics, either stabilizing the binding of the substrate, or interfering with the dynamical ensemble thus preventing substrate binding (1).  The measurement of protein long range structural vibrations associated with conformational fluctuations is challenging due to: a broad continuous density of states laying in a still underdeveloped spectral region, (10-200 cm-1, 0.03 – 6.00 THz) and the overlap of the vibrational energies with liquid water excitations(2).  Using terahertz micropolarimetry on protein crystals we are able to isolate protein long range vibrations and observe that the direction of motions switches with inhibitor binding (3-5).  We have developed a number of different THz techniques to measure the protein vibrations as well as a computational methodology for simulating the spectra (6, 7).  In this talk, I will provide an overview of attempts to measure long range vibrations in proteins, how our current measurements and calculations provide insight into why standard approaches fail, and our approach to investigate if/how structural vibrations provide a control mechanism for protein function.   

1.         Gunasekaran K, Ma BY, & Nussinov R (2004) Is allostery an intrinsic property of all dynamic proteins? Proteins 57(3):433-443.

2.         Falconer RJ & Markelz AG (2012) Terahertz Spectroscopic Analysis of Peptides and Proteins. Journal of Infrared Millimeter and Terahertz Waves 33(10):973-988.

3.         Acbas G, Niessen KA, Snell EH, & Markelz AG (2014) Optical measurements of long-range protein vibrations. Nat Commun 5:3076.

4.         Niessen KA, et al. (2017) Moving in the Right Direction: Protein Vibrational Steering Function. Biophys. J. 112(5):933-942.

5.         Niessen K, Xu M, & Markelz AG (2015) Terahertz optical measurements of correlated motions with possible allosteric function. Biophysical Reviews 7:201-216.

6.         Niessen KA, et al. (2019) Protein and RNA dynamical fingerprinting. Nat Commun 10(1):1026.

7.         Niessen K, Deng Y, & Markelz AG (2019) Near-field THz micropolarimetry. Opt. Express 27(20):28036-28047.