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

肌肉组织经历不断的重塑，以适应其性能的机械需求和（病理）生理线索。MuRF1是一种肌肉特异性E3泛素连接酶，靶向肌肉肌节的丝状组分，并构成该组织翻转的主要分解代谢途径，因此具有高度的生物医学相关性。基于该CRC的综合专业知识，我们将采用X射线晶体学，生物物理学，计算和生物化学方法来研究MuRF1对丝状蛋白的分子靶向作用。这项工作将揭示MuRF1在肌原纤维中的作用机制及其调节原理。我们的首要目标是了解细胞如何解构其细胞骨架结构，以肌节蛋白成分为代表的例子。

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.