Millisecond time-resolved low-angle x-ray fibre diffraction: a powerful, high-sensitivity technique for modelling real-time movements in biological macromolecular assemblies

The modern post-Genomic era heralds the elucidation of many thousands of protein and nucleic acid structures by X-ray crystallography and other techniques. But knowledge of individual macromolecular structures is often not enough. In some cases such macromolecules function as components of much larger molecular assemblies, some of which are filamentous in nature. Striated muscle is a particularly wellordered example of an organised macromolecular assembly and, in addition, it is dynamic; it functions as a mechanical motor using molecular movements which occur in a millisecond timescale. It, therefore, provides a good test case for the development of structural methods. Here we show that time-resolved, lowangle, X-ray fibre diffraction can be used to follow the molecular movements in contracting muscle in real time and with high spatial sensitivity. More generally, the techniques discussed here can be applied to any uniaxially ordered macromolecular assembly