分子伴侣

分子伴侣是最近十几年才发现的一类非常保守的蛋白家庭。它与酶的作用方式类似，能和某些不同的多肽链非特异性结合，催化介导蛋白质特定构象的形成，参与体内蛋白质的折叠、装配和转运，但又不构成其结构的一部分。这类保守的蛋白家族大致可分为四类，广泛存在于生物体中。其中研究得最多的是热休克蛋白。实际上，分子伴侣是一种蛋白质分子构象的协助者，主要参与蛋白质次级结构的形成。     

分子伴侣的功能和应用

本文综述了分子伴侣的分类、功能、作用机理、研究现状及应用前景。分子伴侣是在生物大分子的折叠、组装、转运及降解等过程中起协助作用,参与协助抗原的呈递和遗传物质的复制、转录及构象的确立,但自身并不发生任何变化的一大类广泛存在于生物体内的蛋白质分子。随着对分子伴侣的进一步研究和相关知识的不断深入,分子伴侣在生物产品开发、物种改良、抗衰老,疾病预防、诊断和治疗以及环境监测方面具有广阔的前景。     

分子伴侣介导的细胞自噬作用机制及其功能

分子伴侣介导的细胞自噬(chaperone-mediated autophagy,CMA)是通过溶酶体途径选择性降解胞质中带KFERQ-序列的蛋白质。CMA不仅为细胞在持久饥饿状态下提供能量,还在氧化性损伤保护、维持细胞内环境稳态等方面发挥作用。此外,CMA功能障碍还与某些疾病的发生有关。该文简要综述了这方面的研究进展。     

线虫中的小分子热休克蛋白HSP12.1具有类分子伴侣活性

很多种类的小分子热休克蛋白(small heat shock protein,sHSP)都能在胁迫条件下抑制蛋白质的聚集,显示出了类分子伴侣活性,这种活性是ATP非依赖型的.从已经进行的实验发现,线虫C.elegans中最小的小分子热休克蛋白家族成员HSP12.1具有类分子伴侣活性,以胰岛素、乙醇脱氢酶和溶菌酶做底物发现HSP12.1能够一定程度地抑制底物的热聚集,虽然这种活性较一些经典的分子伴侣蛋白(线虫中的HSP16.1)要低.与此不同,另外3种和其分子质量相近的sHSP12s(HSP12.2、HSP12.3和HSP12.6)却没有检测出这样的类分子伴侣活性,虽然它们在一级结构上有很高的相似性.另外,在大肠杆菌中表达HSP12.1蛋白能够提高细菌在高温环境下的生存率,45℃处理后的生存率比未表达HSP12.1的菌高4倍左右,不过在线虫中是否发挥同样的功能还不是很清楚.从研究结果来看,C端“尾巴”结构域对sHSP发挥类分子伴侣活性不是必要的,在HSP12.1中没有C端“尾巴”结构域也有类分子伴侣活性就证明了这一点.N端结构域可能在发挥类分子伴侣活性中发挥比较重要的作用,当然α-crystallin结构域也可能参与到发挥这样的功能当中.     

辅助伴侣分子Cdc37蛋白的研究进展

细胞分裂周期蛋白Cdc37最初是在芽殖酵母中发现的细胞周期相关蛋白。随后的研究表明Cdc37具有伴侣分子活性,可以特异地募集一系列的蛋白激酶结合到热激蛋白90（Hsp90）上,形成特定的分子伴侣复合体,参与维持蛋白的稳定性和激酶活性。Cdc37参与了细胞内的多项生命活动,在细胞周期、信号转导和基因表达中都起着重要的作用。由于Cdc37在肿瘤组织中特异性地高表达,使其成为肿瘤治疗中一个重要的分子靶点。     

玉米细胞质分子伴侣Hsp70的ATPase活性

玉米胚乳细胞中纯化的细胞质Ｈｓｐ７０蛋白有低水平的ＡＴＰａｓｅ 活性,它在５０ ℃、ｐＨ５ ．８ 、２０ ｍｍｏｌ／Ｌ的ＫＣｌ 条件下活性最高,Ｃａ２＋和Ｍｇ２＋ 抑制其活性。大肠杆菌ＤｎａＪ蛋白能将玉米细胞质Ｈｓｐ７０ 的ＡＴＰａｓｅ 活性提高６倍,而ＧｒｐＥ 蛋白对其影响很小。８ 种不同的人工合成多肽均能刺激该蛋白的ＡＴＰａｓｅ 活性,增加幅度从２ ．５ 倍到１０ 倍不等。亲水性不同的氨基酸对Ｈｓｐ７０ 的ＡＴＰａｓｅ 活性影响不同。玉米细胞质Ｈｓｐ７０ 是一个三磷酸核苷酸酶,除ＡＴＰ 外,它还能催化ＵＴＰ、ＧＴＰ、ＣＴＰ和ＩＴＰ的水解     

基因工程创造新的植物雄性不育系研究的新进展

报道了利用基因工程方法创造植物雄性不育系,恢复系及不育系的筛选和保留的研究成果。     

玉米细胞质分子伴侣Hsp70的ATPase活性

玉米胚乳细胞中纯化的细胞质Ｈｓｐ７０蛋白有低水平的ＡＴＰａｓｅ活性,它在５０℃、ＰＨ５．８、２０ｍｍｏｌ／Ｌ的ＫＣｌ条件下活性最高,Ｃａ＾２＋和Ｍｇ＾２＋抑制其活性。大肠杆菌ＤｎａＪ蛋白能将玉米细胞质Ｈｓｐ７０的ＡＴＰａｓｅ活性提高６倍,而ＧｒｐＥ蛋白对其影响很小。８种不同的人工合成多肽均能刺激该蛋白折ＡＴＰａｓｅ活性,增加幅度从２．５倍到１０倍痫水性不同的氨基酸对Ｈｓｐ７０的ＡＴＰａｓｅ活性影响     

生物的热休克反应研究进展

介绍了生物应激反应的基本概念、基本知识、研究概况、热休克蛋白的作用及与细胞凋亡的关系。     

Structural and functional homology between periplasmic bacterial molecular chaperones and small heat shock proteins

Abstract The periplasmic Yersinia pestis molecular chaperone Caf1M belongs to a superfamily of bacterial proteins for one of which (PapD protein of Escherichia coli ) the immunoglobulin-like fold was solved by X-ray analysis. The N-terminal domain of Caf1M was found to share a 20% amino acid sequence identity with an inclusion body-associated protein IbpB of Escherichia coli . One of the regions that was compared, was 32 amino acids long, and displayed more than 40% identity, probability of random coincidence was 1.2 × 10⁻⁴. IbpB is involved in a superfamily of small heat shock proteins which fulfil the function of molecular chaperone. On the basis of the revealed homology, an immunoglobulin-like one-domain model of IbpB three-dimensional structure was designed which could be a prototype conformation of sHsp's. The structure suggested is in good agreement with the known experimental data obtained for different members of sHsp's superfamily.     

To find the road traveled to tumor immunity: the trafficking itineraries of molecular chaperones in antigen-presenting cells

Molecular chaperones, both endoplasmic reticulum and cytosol derived, have been identified as tumor rejection antigens; in animal models, they can elicit prophylactic and therapeutic immune responses against their tumor of origin. Chaperone immunogenic activity derives from three principal characteristics: they bind an array of immunogenic (poly)peptides, they can be efficiently internalized by professional antigen-presenting cells, and once internalized, they traffic to a subcellular compartment(s) where peptide release can occur. Within the antigen-presenting cell, chaperone-derived peptides can be assembled onto major histocompatibility class I molecules for presentation at the antigen-presenting cell surface, thereby yielding the requisite and specific CD8⁺ T-cell responses that contribute to the process of tumor rejection. Though it is clear that chaperones, in particular GRP94 (gp96), calreticulin and Hsp70, can elicit cellular immune responses, the subcellular basis of chaperone processing by antigen-presenting cells remains mysterious. In this review, we discuss recent reports describing the identification of a chaperone internalization receptor and the physiological release of chaperones from necrotic cells, and we present views on the trafficking pathways within antigen-presenting cells that may function to deliver the chaperone-associated peptides to subcellular organelles for their subsequent exchange onto major histocompatibility complex molecules.     

Hsp70 molecular chaperones and Parkinson's disease

Because over expression of Hsp70 molecular chaperones suppresses the toxicity of aberrantly folded proteins that occur in Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis, and various polyQ‐diseases (Huntington's disease and ataxias), Hsp70 is garnering attention as a possible therapeutic agent for these various diseases. Here, I review progress in this fascinating field of molecular chaperones and neurodegeneration and describe our current understanding of the mechanisms by which Hsp70 protects cells from the PD‐related protein called alpha‐synuclein (α‐syn). © 2009 Wiley Periodicals, Inc. Biopolymers 93: 218–228, 2010. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com     

The role of HSP90 molecular chaperones in hepatocellular carcinoma

Misfolded proteins have enhanced formation of toxic oligomers and nonfunctional protein copies lead to recruiting wild-type protein types. Heat shock protein 90 (HSP90) is a molecular chaperone generated by cells that are involved in many cellular functions through regulation of folding and/or localization of large multi-protein complexes as well as client proteins. HSP90 can regulate a number of different cellular processes including cell proliferation, motility, angiogenesis, signal transduction, and adaptation to stress. HSP90 makes the mutated oncoproteins able to avoid misfolding and degradation and permits the malignant transformation. As a result, HSP90 is an important factor in several signaling pathways associated with tumorigenicity, therapy resistance, and inhibiting apoptosis. Clinically, the upregulation of HSP90 expression in hepatocellular carcinoma (HCC) is linked with advanced stages and inappropriate survival in cases suffering from this kind of cancer. The present review comprehensively assesses HSP90 functions and its possible usefulness as a potential diagnostic biomarker and therapeutic option for HCC.     

热激蛋白70研究进展

热激蛋白70（HSP70）是广泛存在且高度保守的蛋白,作为伴侣分子能够促进蛋白折叠;HSP70可以通过阻止细胞色素c从线粒体释放,与凋亡诱导因子结合使其不能入核,或者抑制JNK激酶活性调节细胞凋亡;HSP70可以调节细胞周期进程,促进细胞生长,阻止细胞衰老;免疫功能研究表明HSP70是有效的免疫佐剂,可激发抗原特异性的CTL反应,同时细胞外HSP70和膜结合HSP70可激发非特异性免疫反应。     

植物胞质雄性不育及育性恢复的分子机制研究进展(综述)

本文从与雄性不育有关的线粒体基因引起雄性不育的机理、雄性不育育性恢复机制以及育性恢复基因的克隆等方面,介绍国内外对植物细胞质雄性不育分子机理的研究进展,并对今后的研究进行讨论。     

The role of molecular chaperones in human misfolding diseases

Human misfolding diseases arise when proteins adopt non-native conformations that endow them with a tendency to aggregate and form intra- and/or extra-cellular deposits. Molecular chaperones, such as Hsp70 and TCP-1 Ring Complex (TRiC)/chaperonin containing TCP-1 (CCT), have been implicated as potent modulators of misfolding disease. These chaperones suppress toxicity of disease proteins and modify early events in the aggregation process in a cooperative and sequential manner reminiscent of their functions in de novo protein folding. Further understanding of the role of Hsp70, TRiC, and other chaperones in misfolding disease is likely to provide important insight into basic pathomechanistic principles that could potentially be exploited for therapeutic purposes.