The Giant Cytoskeletal Protein Obscurin acts as a Variable Force Resistor

Abstract

Obscurin is a giant cytoskeletal protein that is expressed in a wide variety of cells. This protein is highly modular and functions, in part, by connecting distal regions of the cell through individual obscurin domains binding to specific protein targets. Force resistance is intrinsic in this type of protein organization; as the obscurin targets move relative to each other, the obscurin linker by necessity compresses and expands. Work on the similar protein titin suggests that these long modular proteins intrinsically resist this type of motion through an enthalpic-entropic spring mechanism. Here, we study whether obscurin also behaves through this mechanism. Through the use of NMR, SAXS, and SMD, we find that different segments of obscurin behave differently to stretch. Some obscurin segments (for instance Ig34-39) are moderately rigid relative to each other, and this results in a steeper distance/work slope when the these domains are stretched. In contrast, other domains (Ig58-59) show no interaction with their neighbors. These domains stretch more like a traditional pure entropic spring.