Towards Molecular movies of Biomolecules in action with X-Ray Free Electron Lasers

by Prof. Petra Fromme (Arizona State University)

Tuesday 13 May 2025, 13:00 → 14:00 Europe/Berlin

XHQ / E1.173 (European XFEL)

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 proteins including Photosystem I and II as well as protein drug targets [6-10]. The EuXFEL with the highest performance of all 5 large XFELs plays an important role in these discoveries [11-13]. Experiments on the proof of principle for time resolved serial femtosecond crystallography [14-20] 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 [21-23] and report on the new development of compact X-ray Free Electron Lasers at Arizona State University [24].

 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] Gisriel, C.; Coe, J.;  Letrun, R.;  Yefanov, O. M.;  Luna-Chavez, C.; et al  (2019) Nature Communications 10(1), 5021

[12] Yefanov, O., Oberthür, D., Bean, R., et al  Structural Dynamics, 6(6), p.064702.

[13]  Schmidt, M. et al. Res Sq (2023).

[14] Aquila,A, Hunter,MS, Doak,RB, et al HN Optics Express 2012, 20 (3), 2706-16

[15] Kupitz, C, Basu, S, Grotjohann, I et al Nature 2014, 513, 261-5

[16] Tenboer, J., Basu, S., Zatsepin, N. et al Science 2014, 346, 1242-1246

[17] Pande, K., Hutchison, C.D.M., Groenhof, G., Science 2016 , 352(6286), 725-729.

[18] Stagno, J.R., Liu, Y., Bhandari, Y.R., et al Nature 2017,  541(7636), 242-246.

[19] Kupitz, C., Olmos, J.L., Jr., Holl, M. et al Struct Dyn, 2017,  4(4), 044003

[20] Hunter, M.S. & Fromme, P. Methods 55, 387-404 (2011).
[21] Pandey, S. et al. IUCrJ 8, 878-895 (2021).

[22] Zook, J. et al. Structure 28, 540-547 e3 (2020).

[23] Jernigan, R.J. et al. Structure 31, 138-151 e5 (2023).

[24] Graves, W., Fromme, P., Holl, M., et al. (2020) Bulletin of the American Physical Society.

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