Molecular determinants of the catalytic and scaffolding functions of the E3 ubiquitin ligase MuRF1 in the muscle sarcomere (C07)

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The muscle tissue undergoes constant remodelling to adapt its performance to mechanical demands and (patho)physiological cues. MuRF1, a muscle-specific E3 ubiquitin ligase, targets filamentous components of the muscle sarcomere in situ and constitutes a primary catabolic pathway for the turn-over of this tissue, thereby being of high biomedical relevance. Building on the combined expertise of this CRC, we will employ X-ray crystallography, biophysical, computational and biochemical methods to study the molecular targeting of filamentous proteins by MuRF1. This work will reveal the mechanistic mode of action of MuRF1 in the myofibril and the principles of its regulation. Our overarching aim is to understand how the cell deconstructs its cytoskeletal architectures by using sarcomere protein components as representative examples.