Solution structure of multi-domain protein ER-60 studied by aggregation-free SAXS and coarse-grained-MD simulation

Multi-domain proteins (MDPs) show a variety of domain conformations under physiological conditions, regulating their functions through such conformational changes. One of the typical MDPs, ER-60 which is a protein folding enzyme, has a U-shape with four domains and is thought to have different domain conformations in solution depending on the redox state at the active centres of the edge domains. In this work, an aggregation-free small-angle X-ray scattering revealed that the structures of oxidized and reduced ER-60 in solution are different from each other and are also different from those in the crystal. Furthermore, structural modelling with coarse-grained molecular dynamics simulation indicated that the distance between the two edge domains of oxidized ER-60 is longer than that of reduced ER-60. In addition, one of the edge domains has a more flexible conformation than the other.

Automated summary

Multi-domain proteins exhibit various domain conformations under physiological conditions to regulate their functions through conformational changes. ER-60, a typical MDP protein folding enzyme, is found to have different domain conformations in solution depending on the redox state, with oxidized and reduced ER-60 structures differing from each other. Structural modeling with coarse-grained molecular dynamics simulation indicates that the distance between the two edge domains of oxidized ER-60 is longer and one edge domain has a more flexible conformation compared to reduced ER-60.