分子内分子伴侣--Pro肽在蛋白质折叠中的作用

在体内,许多蛋白质,如很多胞外蛋白酶、某些多肽激素等都以含前导肽的前体形式合成,前导肽在蛋白质折叠中具有分子伴侣的功能。为了与一般意义上的分子伴侣相区别,人们将对蛋白质折叠有帮助的前导肽称为分子内分子伴侣,分子内分子伴侣帮助蛋白质在折叠过程中克服高的能量障碍,某些蛋白质的分子内分子伴侣甚至促进其在氧化性折叠中二硫键的正确配对。     

分子伴侣及其在蛋白质折叠中的作用研究进展

蛋白质折叠是一个复杂的、动态的过程,蛋白质的折叠不是自发的,需要其他物质的帮助.了解分子伴侣在蛋白质折叠过程中的的作用,有助于进一步研究蛋白质折叠机制.本文介绍了分子伴侣及其分类,重点综述了各类分子伴侣在蛋白质折叠中的机制,并提出了研究分子伴侣在蛋白质折叠中的作用的重要意义.     

分子伴侣在蛋白质折叠中的作用

分子伴侣主要由三个高度保守的蛋白质家族组成,这三个家族的成员广泛分布于原核和真核细胞中。TCP1复合物是真核细胞细胞溶质内的伴侣蛋白。分子伴侣在蛋白质折叠过程中防止多肽链形成聚集物或无活性结构,提高正确折叠率。本文重点讨论Stress-70家族蛋白质和伴侣蛋白协助蛋白质折叠过程中的协同性以及伴侣蛋白GroEL和GroES的作用机理。     

药物分子伴侣: 蛋白质折叠运输缺陷的新疗法

大量遗传性疾病的发生是由于基因突变引起蛋白质错误折叠而不能运输到作用位点,从而导致功能缺陷．近年来兴起的药物分子伴侣是恢复蛋白质折叠运输缺陷的新疗法,这类化合物一般为目的蛋白的底物类似物、受体配基或酶抑制剂等化学小分子,具细胞通透性,能在内质网中特异性识别并结合突变蛋白,校正并稳定其正确构象,协助其运输到正确位点,直接恢复突变蛋白功能,可治疗各种南蛋白质折叠运输缺陷导致的内分泌及代谢疾病．目前已报道的由药物分子伴侣恢复功能的突变蛋白主要为质膜蛋白及细胞器蛋白,如ATP结合盒转运蛋白、G-蛋白耦联受体及溶酶体酶等．大量的细胞及动物实验结果显示了药物分子伴侣的临床应用前景广阔,目前已有一例临床实验获得了成功．     

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

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。     

新生肽链折叠的新概念

本文介绍近几年来才形成的“新生肽折叠”的新概念,即在核糖体上合成的多肽链成熟为具有特定空间结构和全部生物活力的功能蛋白质的全过程往往不是自发进行的,需 是需要细胞内已经存在的其他蛋白质,分子伴侣和折叠酶的帮助才能完成,文中还简述了分子伴侣和折叠的研究现状。     

GroEL的耗能分子伴侣机制

双环结构Gro EL及其辅分子伴侣Gro ES是目前研究得最深入的分子伴侣.然而,Gro EL/Gro ES帮助蛋白质折叠的一些关键理化机制,尤其是水解ATP,Gro EL发生构象改变,能否主动调节蛋白质错误折叠中间体的构象,以促进错误折叠中间体的复性,仍然存在争议.结合本研究组近年的工作,作者着力介绍Gro EL促进蛋白质折叠的主动解折叠机制.     

蛋白质折叠与装配研究新进展

蛋白质折叠与装配成天然状态的机制,过去根据离体复性实验观察认为是自组装,而近几年来的研究表明体内蛋白质的折叠 与装配并非如此,而是常常依赖于其它辅助因子和ＡＴＰ水解供能,为辅助性组装。这些辅助因子基本可概括为分子内伴侣、酶类和分子伴侣三大类。     

分子伴侣研究概况

分子伴侣主要是在进化上高度保守的热休克蛋白的几个家族。从细菌到哺乳动物,分子伴侣对体内蛋白质的折叠、运输和组装都起到非常重要的作用。本文简要地概述了分子伴侣的组成、它们在蛋白质折叠中的作用以及它们在生物工程下游处理过程中的应用情况。     

Recent advances in the study of Kaposi's sarcoma-associated herpesvirus replication and pathogenesis

It has now been over twenty years since a novel herpesviral genome was identified in Kaposi's sarcoma biopsies. Since then, the cumulative research effort by molecular biologists, virologists, clinicians, and epidemiologists alike has led to the extensive characterization of this tumor virus, Kaposi's sarcoma-associated herpesvirus(KSHV; also known as human herpesvirus 8(HHV-8)), and its associated diseases. Here we review the current knowledge of KSHV biology and pathogenesis, with a particular emphasis on new and exciting advances in the field of epigenetics. We also discuss the development and practicality of various cell culture and animal model systems to study KSHV replication and pathogenesis.     

The structure, reproduction and taxonomy of Vidalia and Osmundaria (Rhodophyta, Rhodomelaceae)

Comprises species occurring mostly in subtidal habitats in tropical, subtropical and warm-temperate areas of the world. An analysis of the type species, V. spiralis (Sonder) Lamouroux ex J. Agardh, a species from Australia, establishes basic characters for distinguishing species in the genus. These characters are (1) branching patterns of thalli, (2) flat blades that may be spiralled on their axis, (3) width of the blade, (4) primary or secondary derivation of sterile and fertile branchlets and (5) position of sterile and fertile branchlets on the thalli. Application of the latter two characters provides an important basic method for separation of species into three major groups. Osmundaria , a genus known only in southern Australia, was studied in relation to Vidalia , and its separation from the Vidalia assemblage is not accepted. Species of Vidalia therefore are transferred to the older genus name, Osmundaria. Two new species, Osmundaria papenfussii and Osmundaria oliveae are described from Natal. Confusion in the usage of the epithet, Vidalia fimbriala Brown ex Turner has been clarified, and Vidalia gregaria Falkenberg, described as an epiphyte on Osmundaria pro/ifera Lamouroux, is revealed to be young branches of the host, Osmundaria prolifera.     

New or rare chromosome counts in Artemisia L. (Asteraceae, Anthemideae) and related genera from Kazakhstan

Fifteen chromosome counts of six Artemisia taxa and one species of each of the genera Brachanthemum, Hippolytia, Kaschgaria, Lepidolopsis and Turaniphytum are reported from Kazakhstan. Three of them are new reports, two are not consistent with previous counts and the remainder are confirmations of very scarce (one to four) earlier records. All the populations studied have the same basic chromosome number, x = 9, with ploidy levels ranging from 2x to 6x. Some correlations between ploidy level, morphological characters and distribution are noted.     

肝癌中HBV和HCV基因和抗原的分布及意义

采用原位分子杂交方法检测HCV RNA及HBV X基因;采用免疫组织化学方法研究HCV核心抗原,非结构区C33c抗原及HBxAg在肝细胞肝癌中的定位及分布.结果表明(1)HCV RNA、HBV X基因在肝细胞肝癌组织检出率分别为40%(55/136)和82%(112/136).HCV RNA定位于癌细胞的胞浆内,阳性细胞呈散在、灶状及弥漫分布三种形式;HBV X基因在肝癌细胞中的分布呈胞浆型、核型及核浆型,阳性细胞也呈上述三种分布形式;(2)HCV C33c抗原、核心抗原在肝细胞肝癌中的阳性率为81%(133/164)及86%(141/164).C33c抗原定位于癌细胞及肝细胞的胞浆内;核心抗原既定位于癌细胞核中,又可定位于胞浆中.C33c抗原阳性细胞以灶状分布为主;而核心抗原阳性细     

Selection with two alleles and complete dominance

For a plant selection model with frequency-independent viabilities, fertilities and selfing rates, it is shown that apart from global fixation, for certain parameter combinations a protected polymorphism and facultative fixation (either allele may become fixed according to initial frequencies) may both occur. Facultative fixation requires different selling rates for the dominant and recessive type. Protection of the polymorphism requires resource allocation for male and female function. In this connection the problem of purely genetically caused population extinction is discussed.
For general frequency dependence and regular segregation, the chances for establishment of a completely recessive gene are compared to those of a completely dominant gene. It is proven that the process of establishment of the recessive gene, despite a fitness advantage, may be considerably endangered by drift effects if random mating prevails. The recessive gene may reach the same effectivity in establishment as a dominant gene, only if the recessive homozygote mates exclusively with its own type during the period of establishment.