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| Janos Hajdu - | |
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Much of what we know about the detailed structure of biomolecules,
including proteins, DNA, and RNA, has come through the use of X-ray
diffraction. Conventional synchrotron radiation catalyzed
revolutionary advances in this field during the past two decades,
enabling the study of larger and more complex systems at increasingly
high levels of resolution and on smaller (often micron-sized) crystals.
The key to this great success has been the use of Bragg diffraction from
the millions of oriented copies of molecules that are well aligned in a
single crystal. However, there are classes of proteins (as well as many
other types of materials) that are difficult or impossible to crystallize,
including membrane proteins and many glycoproteins, for which structure
determination at atomic resolution or even near-atomic resolution would
be invaluable.
Theoretical studies and simulations predict that with a very short, very
intense coherent X-ray pulse, a single diffraction pattern may be recorded
from a large macromolecule, a virus, or a cell without the need for
crystalline periodicity (Neutze et al., 2000; Jurek et al., 2004a,b;
Hau-Riege et al., 2004a). A three-dimensional data set could be assembled
from such patterns when copies of a reproducible sample are exposed to the
beam one by one (Huldt et al. 2003). The over-sampled diffraction pattern
should permit phase retrieval and hence structure determination (Miao et
al., 2001; 2002; 2003; 2004; Robinson et al., 2001; Marchesini et al.,
2003a,b; Hau-Riege et al., 2004b). Free-electron lasers and other
laser-based coherent radiation sources offer the possibility of producing
the requisite pulse structure, and may therefore permit revolutionary
advances in this area. However, the challenges in carrying out such an
experiment are formidable, and will engage an interdisciplinary approach
drawing upon structural biology, atomic and plasma physics, mathematics,
statistics, and X-ray laser physics. The potential for breakthrough science
is great with impact not only in the biological areas but wherever
structural information at or near atomic resolution on the nanoscale
is valuable.
References:
Hau-Riege, S.P., R.A. London, and A. Szöke, Phys. Rev. E 69, 051906 (2004).
Hau-Riege, S.P., Szöke H., Chapman, N.H., Szöke A., Marchesini, S.,
Noy, A., Ho , H., Howells, M., Weierstall, U., Spence, J., Acta
Crystallographica A60, 294-305 (2004b).
Huldt, G., Szöke A., Hajdu, J., J. Struct. Biol. 144, 219-227, (2003).
Jurek, Z. G. Faigel, and M. Tegze, Euro. Phys. J. D 29, 217-229 (2004a).
Jurek, Z., G. Oszlanyi and G. Faigel, Europhys Lett., 65, 491-497, (2004b).
Marchesini, S., Chapman, H. N., Hau-Riege, S. P., London, R. A., Szöke A.,
Opt. Express 11 (19), 2344-2353, (2003a).
Marchesini, S., He, H., Chapman, H. N., Hau-Riege, S. P., Noy, A., Howells, M. R.,
Weierstall, U., Spence, J. C. H., Phys. Rev. B 68 (114), 140101, (2003b).
Miao, J., Hodgson, K., Sayre, D., Proc. Natl. Acad. Sci. USA 98 (12), 6641-6645, (2001).
Miao, J., Ishikawa, T., Johnson, B., Anderson, E. H., Lai, B., Hodgson, K. O.,
Phys. Rev. 89, 088303, (2002).
Miao, J., Hodgson, K. O., Ishikawa, T., Larabell, C. A., LeGros, M. A., Nishino, Y.,
Proc. Natl. Acad. Sci. USA, 100 (1), 110-112, (2003).
Miao, J., H.N. Chapman, J. Kirz, D. Sayre and K.O. Hodgson, Annu. Rev. Biophys.
Biomol. Struct. 33, 157-176 (2004).
Neutze, R. Wouts, D. van der Spoel, E. Weckert, and J. Hajdu, Nature, 406, pp. 752-757 (2000).
Robinson, I. K., Vartanyants, I. A., Williams, G. J., Pfeifer, M. A., Pitney, J. A.,
Phys. Rev. Lett., 87 (19), 195505, (2001).
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