Speaker
Description
" Molecular movies of Biomolecules in action with X-Ray Free Electron Lasers and status on building the world’s first compact XFEL”
Petra Fromme
The Biodesign Center for Applied Structural Discovery and School of Molecular Sciences, Tempe, Arizona 85287- 5001
petra.fromme@asu.edu
Biological processes are highly dynamic, while most of the structures of biomolecules determined by X-ray crystallography and cryo-EM represent a static picture of the molecule frozen in time and space. Serial Femtosecond crystallography (SFX) provides a novel concept for structure determination, where X-ray diffraction “snapshots” are collected from a fully hydrated stream of nanocrystals, using femtosecond pulses at high energy X-ray free-electron lasers [1,2]. The femtosecond pulses from XFELs are so strong that they destroy any sold material but they are shorter than the time-scale of most damage processes, thereby femtosecond crystallography overcomes the problem of X-ray damage in crystallography [3]. Fs crystallography extends to atomic resolution [4,5] and has been applied to important membrane protein drug targets crystallized in lipidic environments [6-10]. Experiments on the proof of principle for time resolved serial femtosecond crystallography [11-16] pave the way for the determination of molecular movies of the dynamics of proteins "at work". In my talk I show highlights of recent structural discoveries with X-ray Free Electron lasers [17-21] and report on the new development of compact X-ray Free Electron Lasers at Arizona State University.
References:
[1] Chapman,HN, Fromme,P, Barty, A. et al Nature 2011, 470, 73-77
[2] Fromme P., Spence JC. Curr Opin Struct Biol 2011, 21: 509-516
[3] Barty,A, Caleman,C, Aquila,A et al. Nature Photonics 2012, 6, 35–40
[4] Boutet S, Lomb L, Williams GJ, et al Science 2012, 337: 362-364
[5] Redecke L, Nass K, Deponte DP. et al Science 2013, 339, 227-30
[6] Liu W, Wacker D, Gati C et al Science 2013, 342: 1521-1524
[7] Weierstall, U, James, D, Wang, C et al. Nature Communications 2014, 5, 3309
[8] Fenalti et al Nature Struc Mol Biol, 2015, 22 (3), 265-268
[9] Zhang, H., Unal, H., Gati, C et al. 2015. Cell 161, 833-844
[10] Kang YY, Zhou XE, Gao X, Nature 2015, 523: p. 561-567.
[11] Aquila,A, Hunter,MS, Doak,RB, et al HN Optics Express 2012, 20 (3), 2706-16
[12] Kupitz, C, Basu, S, Grotjohann, I et al Nature 2014, 513, 261-5
[13] Tenboer, J., Basu, S., Zatsepin, N. et al Science 2014, 346, 1242-1246
[14] Pande, K., Hutchison, C.D.M., Groenhof, G., Science 2016 , 352(6286), 725-729.
[15] Stagno, J.R., Liu, Y., Bhandari, Y.R., et al Nature 2017, 541(7636), 242-246.
[16] Kupitz, C., Olmos, J.L., Jr., Holl, M. et al Struct Dyn, 2017, 4(4), 044003
[17] Hunter, M.S. & Fromme, P. Methods 55, 387-404 (2011).
[18] Pandey, S. et al.. IUCrJ 8, 878-895 (2021).
[19] Zook, J. et al. Structure 28, 540-547 e3 (2020).
[20] Schmidt, M. et al.. Res Sq (2023).
[21] Jernigan, R.J. et al. Structure 31, 138-151 e5 (2023).
