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1.
蛋白质的折叠调控与包涵体的形成   总被引:7,自引:0,他引:7       下载免费PDF全文
新合成的多肽链必须先经折叠和装配后形成特定的三维结构才有活性.分子伴侣和蛋白酶可有效地调控多肽链的正确折叠.然而,在多肽链的折叠过程中,往往也会产生一些折叠异常的蛋白,形成集聚体即包涵体.本文主要对蛋白质的折叠机制、分子伴侣和蛋白酶在折叠中的作用,以及集聚和包涵体的特性、形成机理等做一综述.  相似文献   

2.
概述了蛋白质品质管理中涉及的分子伴侣、激发未折叠蛋白反应(unfolded protein response,UPR)和内质网相关性蛋白质 降解途径(ER-associated degradation,ERAD)等的研究进展,并探讨了该领域存在的问题以及发展前景.指出蛋白质的生命过程经历生成、折叠、组装和降解,每个过程都有严格控制.内质网中,各种蛋白质合成、折叠并经修饰形成具有一定构象的功能性蛋白.其在内质网折叠受阻碍时,未折叠的蛋白聚集,激发UPR,使一系列分子伴侣和蛋白质折叠所需修饰酶类表达上调,帮助其完成折叠和装配.如果这些蛋白仍不能正确折叠,则进入ERAD被降解.  相似文献   

3.
概述了蛋白质品质管理中涉及的分子伴侣、激发未折叠蛋白反应(unfolded protein response, UPR)和内质网相关性蛋白质降解途径(ER-associated degradation, ERAD)等的研究进展,并探讨了该领域存在的问题以及发展前景。指出蛋白质的生命过程经历生成、折叠、组装和降解,每个过程都有严格控制。内质网中,各种蛋白质合成、折叠并经修饰形成具有一定构象的功能性蛋白。其在内质网折叠受阻碍时,未折叠的蛋白聚集,激发 UPR,使一系列分子伴侣和蛋白质折叠所需修饰酶类表达上调,帮助其完成折叠和装配。如果这些蛋白仍不能正确折叠,则进入 ERAD 被降解。  相似文献   

4.
刘泰麟  赵翔  李立新 《安徽农业科学》2012,40(4):1948-1955,2006
概述了蛋白质品质管理中涉及的分子伴侣、激发未折叠蛋白反应(unfolded protein response,UPR)和内质网相关性蛋白质降解途径(ER-associated degradation,ERAD)等的研究进展,并探讨了该领域存在的问题以及发展前景。指出蛋白质的生命过程经历生成、折叠、组装和降解,每个过程都有严格控制。内质网中,各种蛋白质合成、折叠并经修饰形成具有一定构象的功能性蛋白。其在内质网折叠受阻碍时,未折叠的蛋白聚集,激发UPR,使一系列分子伴侣和蛋白质折叠所需修饰酶类表达上调,帮助其完成折叠和装配。如果这些蛋白仍不能正确折叠,则进入ERAD被降解。  相似文献   

5.
变性蛋白质体外复性的方法主要有传统的辅助复性法包括了:稀释法、透析法、超滤法以及蛋白质折叠液相色谱法(PFLC),也有在此基础上模拟体内分子伴侣、折叠酶、人工分子伴侣、反胶束的辅助复性方法。到目前为止,在复性液中添加小分子试剂是提高体外辅助蛋白质复性效率的策略之一。其目的是为了降低蛋白质复性过程中聚集形式的形成,从而促进变性蛋白质向其天然和活性构象的转变。这种方法在一定程度上能够提高蛋白质的复性效率并且得到了长足的发展。为了捕捉变性蛋白质向其活性结构折叠过程的差异性变化规律,明确小分子添加剂对体外辅助蛋白质分子折叠过程的机制,推测一些小分子添加剂辅助蛋白质色谱复性过程中构象的变化规律,为解决包涵体蛋白质难于复性和复性效率低的问题起到指导性的作用。  相似文献   

6.
J蛋白是一类含有J结构域或类J结构域、分子质量为40 k Da左右的蛋白。其主要作用是作为热激蛋白70s的辅助分子伴侣参与新生蛋白质的折叠、蛋白质正确构象的维持、蛋白质的转运、蛋白复合体的组装和解离等过程。鉴于近几年对植物J蛋白的生物学功能研究取得了长足进展,本文在扼要介绍植物J蛋白结构与分类的基础上,重点阐述了植物J蛋白的生物学功能及其分子作用机制,最后对该研究领域作了展望。  相似文献   

7.
DnaJ-like蛋白是一种重要的分子伴侣,调节分子伴侣HSP70的ATP酶活性,并参与新生肽的折叠、装配和运输过程。大量研究表明,DnaJ-like蛋白具有功能多样性,在植物的形态建成、生长发育以及胁迫应答过程中具有极其重要的作用。综述了DnaJ-like蛋白在植物生物与非生物胁迫响应方面的功能及可能的机制,并对未来的研究方向提出了建议。  相似文献   

8.
蛋白质折叠的研究进展   总被引:4,自引:0,他引:4  
关于蛋白质折叠的研究,是生命科学领域的前沿课题之一.根据Anfin-sen原理,蛋白质分子的一级结构决定其高级结构,蛋白质折叠的研究,就是研究蛋白质特定三维空间结构形成的规律、稳定性和与其生物活性的关系.蛋白质分子的氨基酸顺序决定于DNA中的遗传密码,而蛋白质三维空间结构的形成可以说是由折叠密码(folding code),即"第二遗传密码"决定的.因此,研究蛋白质折叠的过程,可以说是破译"第二遗传密码"的过程.  相似文献   

9.
哺乳动物肽聚糖识别蛋白抗菌作用及其机制的研究进展   总被引:1,自引:0,他引:1  
哺乳动物肽聚糖识别蛋白(PGRPs)是一类可识别肽聚糖的免疫激活分子,具有抗菌活性.它的抗菌机制与其他抗菌肽明显不同.最新研究发现,哺乳动物PGRPs通过与肽聚糖结合,激活在细菌中识别胞浆外错误折叠蛋白质分子的CssR-CssS或CpxA-CpxR双部件系统,最终导至细菌死亡.文中总结了肽聚糖识别蛋白的抗菌作用及其机制的相关研究进展.  相似文献   

10.
细菌脂肪酶是一类重要的工业用酶,尤其以来源于假单孢杆菌Pseudomonas与伯克霍尔德菌Burkholderia的脂肪酶应用最为广泛。然而,这类脂肪酶折叠过程中存在一个巨大的能障而无法自发正确折叠。研究发现,这类脂肪酶的编码基因所在操纵子中往往存在一个与其折叠相关的基因,编码一种脂肪酶特异折叠酶。该类蛋白为脂肪酶的立体分子伴侣,可与脂肪酶的折叠中间体相互作用,帮助脂肪酶越过折叠过程中的能量障碍,为其获得正确构象提供必要的空间信息。详细阐述了脂肪酶特异折叠酶的发现、分类、作用机制与应用前景。  相似文献   

11.
Molecular chaperones in the cytosol: from nascent chain to folded protein   总被引:5,自引:0,他引:5  
Efficient folding of many newly synthesized proteins depends on assistance from molecular chaperones, which serve to prevent protein misfolding and aggregation in the crowded environment of the cell. Nascent chain--binding chaperones, including trigger factor, Hsp70, and prefoldin, stabilize elongating chains on ribosomes in a nonaggregated state. Folding in the cytosol is achieved either on controlled chain release from these factors or after transfer of newly synthesized proteins to downstream chaperones, such as the chaperonins. These are large, cylindrical complexes that provide a central compartment for a single protein chain to fold unimpaired by aggregation. Understanding how the thousands of different proteins synthesized in a cell use this chaperone machinery has profound implications for biotechnology and medicine.  相似文献   

12.
Many biological processes are regulated through the selective dephosphorylation of proteins. Protein serine-threonine phosphatases are assembled from catalytic subunits bound to diverse regulatory subunits that provide substrate specificity and subcellular localization. We describe a small molecule, guanabenz, that bound to a regulatory subunit of protein phosphatase 1, PPP1R15A/GADD34, selectively disrupting the stress-induced dephosphorylation of the α subunit of translation initiation factor 2 (eIF2α). Without affecting the related PPP1R15B-phosphatase complex and constitutive protein synthesis, guanabenz prolonged eIF2α phosphorylation in human stressed cells, adjusting the protein production rates to levels manageable by available chaperones. This favored protein folding and thereby rescued cells from protein misfolding stress. Thus, regulatory subunits of phosphatases are drug targets, a property used here to restore proteostasis in stressed cells.  相似文献   

13.
Polypeptides emerging from the ribosome must fold into stable three-dimensional structures and maintain that structure throughout their functional lifetimes. Maintaining quality control over protein structure and function depends on molecular chaperones and proteases, both of which can recognize hydrophobic regions exposed on unfolded polypeptides. Molecular chaperones promote proper protein folding and prevent aggregation, and energy-dependent proteases eliminate irreversibly damaged proteins. The kinetics of partitioning between chaperones and proteases determines whether a protein will be destroyed before it folds properly. When both quality control options fail, damaged proteins accumulate as aggregates, a process associated with amyloid diseases.  相似文献   

14.
Alpha-synuclein (alphaSyn) misfolding is associated with several devastating neurodegenerative disorders, including Parkinson's disease (PD). In yeast cells and in neurons alphaSyn accumulation is cytotoxic, but little is known about its normal function or pathobiology. The earliest defect following alphaSyn expression in yeast was a block in endoplasmic reticulum (ER)-to-Golgi vesicular trafficking. In a genomewide screen, the largest class of toxicity modifiers were proteins functioning at this same step, including the Rab guanosine triphosphatase Ypt1p, which associated with cytoplasmic alphaSyn inclusions. Elevated expression of Rab1, the mammalian YPT1 homolog, protected against alphaSyn-induced dopaminergic neuron loss in animal models of PD. Thus, synucleinopathies may result from disruptions in basic cellular functions that interface with the unique biology of particular neurons to make them especially vulnerable.  相似文献   

15.
Molecular chaperones are a family of unrelated proteins found in all types of cell. They mediate the correct assembly of other polypeptides, but are not components of the mature assembled structures. Chaperones function by binding specifically to interactive protein surfaces that are exposed transiently during many cellular processes and so prevent them from undergoing incorrect interactions that might produce nonfunctional structures. The concept of molecular chaperones originated largely from studies of the chloroplast enzyme rubisco, which fixes carbon dioxide in plant photosynthesis; the function of chaperones forces a rethinking of the principle of protein self-assembly.  相似文献   

16.
The incidence of Alzheimer's disease (AD) and that of prion disorders (PrD) could not be more different. One-third of octogenarians succumb to AD, whereas Creutzfeldt-Jakob disease typically affects one individual in a million each year. However, these diseases have many common features impinging on the metabolism of neuronal membrane proteins: the amyloid precursor protein APP in the case of AD, and the cellular prion protein PrPC in PrD. APP begets the Abeta peptide, whereas PrPC begets the malignant prion protein PrPSc. Both Abeta and PrPSc are associated with disease, but we do not know what triggers their accumulation and neurotoxicity. A great deal has been learned, however, about protein folding, misfolding, and aggregation; an entirely new class of intramembrane proteases has been identified; and unsuspected roles for the immune system have been uncovered. There is reason to expect that prion research will profit from advances in the understanding of AD, and vice versa.  相似文献   

17.
王国强 《安徽农业科学》2010,38(19):9946-9947,9949
根据国内外近年来小分子热休克蛋白的研究概况,对小分子热休克蛋白的分子伴侣功能、稳定细胞结构功能和调节细胞凋亡功能进行综述,并讨论小分子热休克蛋白在生物进化研究中的意义以及应用前景。  相似文献   

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