Single Molecule Förster Resonance Energy Transfer Studies of the Effect of Deglycosylation on the Structure of Immunoglobulin G

Abstract

Obscurin (720-900 kD) is a giant sarcomeric signaling protein that plays a crucial role in the arrangement of the basic contractile unit of muscle. Mutations to Obscurin and to Obscurin binding partners have been linked to human muscle diseases such as hypertrophic cardiomyopathies and muscular dystrophy. These diseases likely occur due to the rescindment of specific molecular interactions necessary for suitable function. The modular arrangement of the independently folding domains of Obscurin allows for select analysis of each of these independent binding events. Here, we present the high-resolution crystal structure of the Obscurin Ig2 domain. This region binds to the extreme Cterminus of MBPC-slow variant, although how it does this is unknown. This structure is a canonical Ig-like fold, consisting of two beta sheets coming together to form a beta sandwich.