Study of complex and macro‐molecular systems using small angle x‐ray scattering (593.1)

Abstract

Understanding the molecular organization of the glomerular filtration assembly is highly desirable that will aid in designing strategies for recovery of this structure in the event of a glomerular injury. Small angle X‐ray scattering (SAXS) is emerging as a powerful tool to understand the complex and multimeric macro‐molecular assemblies in their dynamic environment. We have successfully employed this technique in the recent years to understand structural details of the cytoplasmic domain of Neph1 (a component of the kidney’s filtration system) and its interaction with partner proteins. In the present study, we extended the SAXS based experimental and computational approach to understand the function of cytoplasmic domain of a slit diaphragm protein Nephrin which plays a critical role in maintaining filtration function of the glomerulus. Interestingly, the SAXS analysis suggests that the cytoplasmic domain of Nephrin is structurally similar to the cytoplasmic domain of its closest family member, Neph1. Importantly, the two proteins have been shown to perform similar functions. Additionally, we are the first to determine the solution‐based structure of the motor protein Myo1c and are in a unique position to model the interacting regions of Nephrin and Myo1c using SAXS and molecular modeling. These results will significantly impact the understanding of the molecular organization of the glomerular filtration assembly.Grant Funding Source: NIH Research Grant (R01)