Protein folding dynamics detected by time-resolved synchrotron X-ray small-angle scattering technique

The polypeptide collapse is an essential dynamics in protein folding. To understand the mechanism of the collapse, in situ observation of folding by various probes is necessary. The changes in secondary and tertiary structures in the folding process of globular proteins, whose chain lengths are less than 300 polypeptides, were observed by circular dichrosim and intrinsic fluorescence spectroscopies, respectively. On the other hand, those in protein compactness could be only detected by using time-resolved synchrotron x-ray small-angle scattering technique. The observed dynamics for several proteins with different topologies suggested a common folding mechanism termed "collapse and search" dynamics, in which the polypeptide collapse precedes the formation of the native contact formation. In "collapse and search" dynamics, the most outstanding feature lied in the compactness of the initial intermediates. The collapsed intermediates demonstrated the scaling relationship between radius of gyration (R_g) and chain length with a scaling exponent of 0.35 ± 0.11, which is close to the value (1/3) predicted by mechano-statistical theory for the collapsed globules of polymers in poor solvent. Thus, it was suggested that the initial collapse is caused by the coil-globule transition of polymers. Since the collapse is essential to the folding of larger proteins, further investigations on the collapse likely lead to an important insight into the protein folding phenomena.