Welcome to the machine: a cardiologist's introduction to protein folding and degradation.
Welcome to the machine: a cardiologist's introduction to protein folding and degradation.
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DOI：
10.1161/01.cir.0000041145.30519.6b
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发表时间：
2002-11
期刊：
影响因子：
37.8
通讯作者：
C. Patterson;D. Cyr
中科院分区：
文献类型：
--
作者：
C. Patterson;D. Cyr
心血管系统为维持循环付出的代价正在成为导致磨损的慢性力量的目标。心血管组织经常处于这些应激的损伤危险中，并依赖高度保守的细胞机进行保护。细胞环境适应于检测、修复并在必要时处理受损蛋白质，部分原因是它们对细胞有毒。分子伴侣和泛素-蛋白酶体系统是修复和降解受损蛋白质的机制，但在心血管病理生理学中对这些系统的研究还很少。最近的进展使蛋白质的折叠和降解更接近心血管生物学的前沿。这篇综述讨论了这些进展，并提出了新的模型，将心血管病理生理学和治疗学视为蛋白质动态平衡问题。在大多数情况下，蛋白质折叠所需的所有信息都包含在其主要氨基酸序列中。然而，细胞内的环境特别不利于蛋白质折叠，因为在蛋白质合成过程中发生的限制，以及在拥挤的细胞环境中阻碍折叠的分子间相互作用的可能性。一个进化上古老的系统存在，以防止受损的或新合成的多肽聚集，并提供一个微环境，促进它们适当地折叠成热力学上有利的活性构象。这个系统由分子伴侣组成，分子伴侣存在于每个细胞隔间，用于缓冲和修复受损的蛋白质(表中提供了哺乳动物伴侣的部分清单)。去除蛋白质的机制对细胞功能同样至关重要，而蛋白质降解的机制也同样陈旧。虽然真核生物中存在几种蛋白质破坏途径，但泛素-蛋白酶体系统是蛋白质降解的主要途径，也是调控最严格的途径。查看此表：哺乳动物伴侣及其功能的例子伴侣和泛素蛋白酶体…
The price paid by the cardiovascular system for maintaining circulation is being a target of chronic forces that contribute to wear and tear. Cardiovascular tissues are in constant peril of damage from these stresses, and are dependent on highly conserved cellular machines for protection. The cellular environment is adapted to detect, repair and, if necessary, dispose of damaged proteins, in part because they are toxic to the cell. The molecular chaperone and ubiquitin-proteasome systems are the machinery that repair and degrade damaged proteins, yet little attention has been given to these systems in cardiovascular pathophysiology. Recent advances have brought protein folding and degradation closer to the forefront of cardiovascular biology. This review discusses these advances and presents new models for consideration of cardiovascular pathophysiology and therapeutics as problems of protein homeostasis. In most cases, all the information necessary for a protein to fold is contained in its primary amino acid sequence. The environment within a cell is particularly unfavorable for protein folding, however, because of constraints that occur during protein synthesis and the likelihood of intermolecular interactions that impede folding in a crowded cellular environment. An evolutionarily ancient system exists to prevent damaged or newly synthesized peptides from aggregating and to provide a microenvironment that facilitates their proper folding to a thermodynamically favorable active conformation. This system comprises the molecular chaperones, which are present in every cellular compartment to buffer and repair damaged proteins (the Table provides a partial list of mammalian chaperones). Mechanisms for removing proteins are equally critical to cellular function, and the machinery of protein degradation is similarly archaic. Although several pathways exist for protein destruction in eukaryotes, the ubiquitin-proteasome system is responsible for the majority of protein degradation and is the most tightly regulated pathway. View this table: Examples of Mammalian Chaperones and Their Functions The chaperone and ubiquitin-proteasome …