Protein quality control mechanisms of novel soluble substrates

描述(由申请人提供)：蛋白质质量控制机制是正常细胞健康所必需的，以预防疾病和避免过早衰老。独特的突变蛋白是这些途径的底物，由蛋白质质量控制途径组件识别，通常由蛋白酶体降解。带有微小错义突变的蛋白质可以保留功能，但这些途径的降解可能是发病的基础。蛋白质质量控制底物识别的分子和物理基础还知之甚少，特别是对可溶性胞浆蛋白。这项申请建议使用一个强大的多学科方法来定义蛋白质质量控制途径中的新蛋白质，并阐明底物识别的物理和结构基础。

DESCRIPTION (provided by applicant): Protein quality control mechanisms are required for normal cellular health to prevent disease and avoid premature senescence. Unique mutant proteins are substrates of these pathways, are recognized by protein quality control pathway components and typically degraded by the proteasome. Proteins with subtle missense mutations can retain function yet degradation by these pathways can underlie pathogenesis. The molecular and physical basis of protein quality control substrate recognition are poorly understood, especially for soluble cytosolic proteins. This application proposes to use a powerful multi disciplinary approach to define novel proteins in the protein quality control pathway and elucidate the physical and structural basis of substrate recognition.