Mokry David Z, Abrahão Josielle, Ramos Carlos H I
Instituto de Química, Universidade Estadual de Campinas, Campinas, SP, BR.
An Acad Bras Cienc. 2015 Aug;87(2 Suppl):1273-92. doi: 10.1590/0001-3765201520140671. Epub 2015 Aug 25.
The process of folding is a seminal event in the life of a protein, as it is essential for proper protein function and therefore cell physiology. Inappropriate folding, or misfolding, can not only lead to loss of function, but also to the formation of protein aggregates, an insoluble association of polypeptides that harm cell physiology, either by themselves or in the process of formation. Several biological processes have evolved to prevent and eliminate the existence of non-functional and amyloidogenic aggregates, as they are associated with several human pathologies. Molecular chaperones and heat shock proteins are specialized in controlling the quality of the proteins in the cell, specifically by aiding proper folding, and dissolution and clearance of already formed protein aggregates. The latter is a function of disaggregases, mainly represented by the ClpB/Hsp104 subfamily of molecular chaperones, that are ubiquitous in all organisms but, surprisingly, have no orthologs in the cytosol of metazoan cells. This review aims to describe the characteristics of disaggregases and to discuss the function of yeast Hsp104, a disaggregase that is also involved in prion propagation and inheritance.
蛋白质折叠过程是蛋白质生命历程中的一个关键事件，因为它对于蛋白质的正常功能以及细胞生理功能至关重要。不适当的折叠，即错误折叠，不仅会导致功能丧失，还会导致蛋白质聚集体的形成，蛋白质聚集体是多肽的不溶性聚集体，无论是其本身还是在形成过程中都会损害细胞生理功能。已经进化出多种生物学过程来预防和消除无功能和淀粉样聚集体的存在，因为它们与多种人类疾病相关。分子伴侣和热休克蛋白专门负责控制细胞内蛋白质的质量，具体方式是协助正确折叠以及溶解和清除已形成的蛋白质聚集体。后者是解聚酶的功能，主要由分子伴侣的ClpB/Hsp104亚家族代表，它们在所有生物体中普遍存在，但令人惊讶的是，在后生动物细胞的细胞质中没有直系同源物。本综述旨在描述解聚酶的特性，并讨论酵母Hsp104的功能，Hsp104是一种解聚酶，也参与朊病毒的传播和遗传。
