十一月的报告:蛋白质试管内折叠/蛋白质结构与序列 November Presentations: Protein Folding in vitro / Protein Structure and Sequences |
| 1 |
芳香环支链在球蛋白内的构型 The Conformations of Aromatic Side Chains in Globular Proteins |
大部分的芳香环被发现于蛋白质内部。请问芳香环在蛋白质内部参与何种作用?有证据指出芳香环在蛋白质内部可以移位。这种移位有多快?有多普遍? Most aromatic rings are found in the interior of proteins. What kinds of interactions are aromatic rings involved in within protein interiors? There is evidence in some proteins that the rings can flip. How rapidly? How general is this motion? |
| 2 |
试管内胶原蛋白的再折叠 The in vitro Refolding of Collagen |
类胶原蛋白序列的肽链结构最近刚被核磁共振与x射线衍射光谱所解出。利用氘核磁共振光谱可以监测肽链折叠与结合反应的实际动力学状态以及置换某些甘氨酸的影响。 Short tripeptides with collagen-like sequences have recently been crystallized and their structure solved by X-ray diffraction. Using 2-D NMR it has been possible to follow the actual kinetics of the chain folding and association reaction and the effects of certain glycine substitutions. |
| 3 |
双股、三股、四股的卷曲螺旋 Two Stranded, Three Stranded, Four Stranded Coiled Coils |
卷曲螺旋并不局限于一对,而是受包埋在内的疏水性氨基酸所影响,螺旋股可以形成三体或更高的聚合体。 近期研究更指出序列与三级结构的关系。 Coiled coils are not limited to pairs; depending on the details of the residues at the buried hydrophobic positions, the helices will form trimeric and higher associations. Recent studies reveal the fine points of the relationship between sequence and tertieary associations. |
| 4 |
静电交互作用在卷曲螺旋的折叠、结合与生成 Electrostatic Interations in the Folding, Association and Registration of the Coiled Coils |
虽然肽链间疏水性交互作用很重要,然而带电荷的交互作用也控制,如肌凝蛋白及亮氨酸拉链的结构与卷曲螺旋的聚合。近期的报导指出各个这类离子对在结构稳定性的贡献。 Though the hydrophobic interactions are critical, charged side chains interactions also control the structure and association of coiled/coils in both tropomyosin, and leucine zippers. Recent papers report differing values for the contributions of these ion pairs to stability. |
| 5 |
β旋转是否形成可溶解多肽? Do Beta Turns Form in Soluble Peptides? |
近期对合成肽链的核磁共振研究指出,β旋转可能比想像中更稳定,其可能是形成蛋白质折叠的核心。 Recent NMR studies of synthetic peptides suggest that beta turns may be more stable than expected and might be candidates for protein folding nuclei. |
| 6 |
在球蛋白内的螺旋延伸与终止讯号 Helical Extension and Termination Signals in Globular Proteins |
从序列的分析指出螺旋区的末端有其偏好的残基。在芽孢杆菌核酸酶与T4噬菌体溶菌酶中取代末端残基则会改变螺旋末端的生成。 Analysis of sequences at the ends of helical regions reveal preferred residues. In both Barnase and T4 lysozyme substitutions have been generated which alter the termini of helices in the proteins. |
中段主题——十一月后期 Mid Session Topics - Late November |
| 7 |
原肌红素的再折叠途径 The Refolding Pathway For Apomyoglobin |
氢原子交换与核磁共振被广泛地应用来鉴定原肌红素再折叠的中间产物;这些研究有助于解读各种人类血红素突变种与序列资料。 Hydrogen exchange and NMR have been used to identify intermediates in the refolding of apomyoglobin. This allows interpretation of a variety of human hemoglobin mutants and other sequence data. |
| 8 |
环状交换的多肽链 Circularly Permuted Polypeptide Chains |
氨基酸序列的连续性与连接性有多重要呢?在牛胰岛蛋白脢抑制剂(BPTI)这个希腊钥匙型的β转角蛋白及其他较大的酶,氨端跟羧端被连接起来并产生新的末端,来研究序列交换对折叠的影响。 How important is the continuity and connectedness of amino acid sequences? In BPTI, the Greek key beta barrel proteins and some larger enzymes, the N- and C- termini have been joined together and new physical ends created, to examine the effects of sequence permutation on chain folding. |
| 9 |
T4噬菌体溶菌酶的突变研究 Mutational Studies with T4 Lysozyme |
在各种已知原子级解析度的蛋白质中,T4噬菌体溶菌酶其氨基酸序列突变对其分子构型和折叠稳定度的影响是被研究得最透彻的。 这些实验提供了局部序列与整体的折叠的关系也带来一些有用的惊喜。 Among proteins of known atomic structure, extensive studies of the affects of mutations on the conformation and stability of the folded protein have been carried out with T4 lysozyme. These experiments have yielded both insight into the relationship of local sequence and overall fold, and some useful surprises. |
| 10 |
蛋白质的β折叠 Folding of Beta Sheet Proteins |
近期的研究已开始鉴定出如介白细胞介素或是脂肪酸结合蛋白等蛋白质β折叠的生成的中间产物。 这些实验使用了氕/氘交换配合光谱技术。 Recent studies have begun to identify intermediates in the formation of small beta sheet proteins such as the interleukins and fatty acid binding proteins. These experiments utilize both hygrogen/deuterium exhange combined with spectroscopic procedures. |
| 11 |
萤光素酶的折叠伴随着亚单位交互作用 Coupling of Folding and Subunit Interaction in Luciferase |
许多单体蛋白组合时并非由自然态亚单位形成而是由次单位折叠中间产物形成的。 其中照亮深海鱼类眼睛的细菌萤光素其异双体结构即是大家所熟知的例子。 In many oligomeric proteins assembly proceeds not from native subunits but from folding intermediates of the subunits. One of the best understood cases is the heterdimeric luciferase from the bacteria that illuminate the eyes of deep sea fish. |
| 12 |
细菌视紫红质的折叠与插入 Folding and Insertion of Bacteriorhodopsin |
视觉器官的视紫红质蛋白是少数三维结构被解出来的膜蛋白之一。 几个精良设计的实验即是利用了细菌和哺乳类视蛋白来研究跨膜螺旋如何与细胞膜结合。 One of the very few membrane proteins whose three dimensional structure has been solved is the rhodopsin of the visual system. The best defined experiments on how these transmembrane helices associate within the membrane have been done with the bacterial and mammalin opsin. |
十二月的报告:细胞器之于蛋白质折叠 December Presentations: Cellular Apparatus for Protein Folding |
| 13 |
核醣体上新生链的构型 The Conformations of Nascent Chains on the Ribosome |
刚合成的多肽链在核醣体上是什么构型?核醣体是否参与蛋白质的早期折叠?激发因子的角色为何? What is the conformation of the newly synthesized polypeptide chain as it exits the ribosome? Does the ribosome play a role in early stages of protein folding? What are the roles of Trigger Factor? |
| 14 |
脯氨酸羟化酶在胶原蛋白的链折叠与成熟的功用 Functions of Prolyl Hydroxylases in Collagen Chain Folding and Maturation |
脯氨酸羟化酶负责在新合成的链上产生羟化脯氨酸并被认为参与调节三绞螺旋的生成。 低度脯氨酸羟化是维生素C缺乏的坏血病的分子层级缺陷。 Prolyl hydroxylase is responsible for the formation of hydroxyproline on newly synthesized chains and is thought to be involved in regulating triple helix formation. Underhydroxylation of prolines is the molecular defect in scurvy, vitamin C deficiency. |
| 15 |
脯胺酸异构酶在蛋白质折叠的角色 The Role of Prolyl Isomerase in Protein Folding |
脯胺酸异构化的功能为何?脯胺酸异构酶在细胞内对新合成的多肽链(包括前胶原蛋白)的折叠有何影响?脯胺酸异构酶原本称为亲和素,是环孢菌素这类免疫抑制药剂的目标。 What is the role of proline isomerization and proline isomerase in the folding of newly synthesized polypeptide chains within cells, including pro collagen? Prolyl isomerase, originally called cyclophilin is the target of the cyclosporin class of immunosuppressive drugs. |
| 16 |
菌孔道蛋白的折叠与组合 Folding and Assembly of Bacterial Porins |
菌孔道蛋白是一类膜蛋白,其膜蛋白孔道是由数个大型的β转角而非α螺旋所组成,它的三维结构已被解出。 The porins are a class of membrane proteins making large pores which use large beta barrels rather than alpha helical proteins and whose 3-D structures have been solved. |
| 17 |
参与原核生物双硫键生成的蛋白 Prokaryotic Proteins Involved in Disulfide Bond Formation |
遗传学研究鉴定出一族在细菌中参与硫醇氧化与还原的蛋白,并且认为这些蛋白影响某些蛋白的折叠。 Genetic studies in bacteria have identified a family of proteins involved in reduction and oxidation of thiols, and presumed to be involved in the folding of some proteins. |
| 18 |
双硫键异构酶在内质网所扮演的角色 The Role of Protein Disulfide Isomerase in the Endoplasmic Reticulum |
在真核细胞新合成的多肽链如何产生双硫键并且被送到胞外? How are disulfide bonds formed in newly synthesized polypeptide chains destined for export from eukaryotic cells? |
| 19 |
流感病毒红血球凝集素的胞内折叠与组合 In vivo Folding and Assembly of the Influenza Hemagglutinin |
这个三体病毒外鞘蛋白的胞内组合是一个不错的真核蛋白折叠模型。 The intracellular assembly and maturation of this trimeric viral coat protein is one of the better model systems in eukaryotic cells. |
| 20 |
SecB伴随蛋白在蛋白输出的作用 The secB Chaperonins in Proteins Destined for Export |
一些要被分派到胞外(或是在胞外折叠)的蛋白在合成后必须先保持未折叠,secB是大肠杆菌中用来维持这个状态的蛋白中被研究相当透彻的蛋白。 A number of proteins destined for export (and perhaps folding) outside the cell must be maintained in a non-folded state after synthesis. Some of those are maintained in this state by the secB protein of E.coli, whose mechanism has been studied in considerable detail. |
| 21 |
GroE S伴随蛋白的功能与结构 Structure and Functions of the Eukaryotic Dedicated GroE S Chaperonins |
GroE为一种保留的十四亚单位单体,至少在高温时参与确保新生蛋白链的正确折叠。 A conserved class of 14 subunit oligomers, the GroE chapoeronins, is involved in insuring the correct folding of newly synthesized chains, at least at high temperature. |
| 22 |
GroE帮助蛋白质折叠的机制 The Mechanism of GroE Function in Protein Folding and Asssembly |
伴随蛋白实际上如何帮助蛋白折叠,这个玩偶匣是怎么作用的?ATP水解如何驱动伴随蛋白作用? How does the chaperone actually function in ensuring productive protein folding? How does the Jack in the Box work, how is ATP hydrolysis coupled to chaperone function? |
| 23 |
伴随蛋白在细菌纤毛组合过程中的作用 Chaperonin Function in Bacterial Pilus Assembly |
细菌用纤毛与鞭毛来游泳、附着至另一细胞及运送遗传物质DNA。 形成这种胞器的蛋白要折叠或组合需要一类作用于膜间腔的特殊的伴随蛋白。 Bacteria use extra cellular flagelli and pili for swimming, attaching to other cells and transporting DNA. The folding and assembly of the proteins for these organelles utilize specialized chaperonins some of which function in the bacterial periplasm. |
| 24 |
蛋白质输出输入的通道 Channels for Protein Import and Export |
许多新合成的蛋白必须通过膜层,例如送入腺粒体或内质网的蛋白。一般而言,多肽链必须先保持未折叠。 在一些生物体中形成这类通道的蛋白已被鉴定出来。 Many newly synthesized proteins have to transit a membrane, for example, for import into mitochondria or for entry to the endoplasmic reticulum. In general, the polypeptide chains have to be maintained in an unfolded state. The proteins forming these channels have recently been identified in a number of organisms. |
| 25 |
DNA K(HSP90)类型伴随蛋白的功用 Function of the DNA K (HSP90) Class of Chaperonins |
这类蛋白似乎作用在GroE之前的肽链合成阶段,通常以DNA K、 DNA J以及Grp E.复合体的型态作用。 These appear to interact with newly synthesized chains at an earlier stage in folding than the GroE class, and function as a complex of DNA K, DNA J, and Grp E. |
后期的报告:蛋白质折叠错误与疾病 Later Presentations: Protein Misfolding and Disease |
| 26 |
晶状蛋白与白内障 Lens Crystallins and Cataracts |
晶状体的蛋白“晶状蛋白”有许多不寻常的特色,至少它是高浓度存在。γ-晶状蛋白可在试管内再折叠且其三维立体结构已经被解出。 一些研究者相信这些分子的不正确结合会导致白内障。 The proteins of the lens, crystallins, have a variety of unusual properties, at least at high concentrations. The three-dimensional fold of the Gamma crystallin has been solved and the protein can be refolded in vitro. Some investigators believe incorrect association of these molecules leads to cataracts. |
| 27 |
阿尔采末症的类淀粉体沉积 Amyloid Deposits in Alzheimers Disease |
阿尔采末症的病患的许多组织内有着不可溶的蛋白沉积,一个主要的类型的特色为具有特殊的交叉的β圆柱结构。 Alzheimers patients have insoluble protein deposits in a number of their tissues. A major class are characterized by a distinctive cross beta rod structure.
- 主题 A:阿尔采末多肽的试管内聚合的研究
Topic A: Studies on the in vitro association of the Alzheimer's peptide.
- 主题 B:类淀粉斑在活体内的生成
Topic B: Formation of amyloid plaques in vivo.
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| 28 |
蛋白感染素疾病其蛋白质结合现象 Prion Diseases as Protein Association Phenomoma |
越来越多的证据指出蛋白感染素疾病(如疯牛病)是因为蛋白质结合过程中其构型产生不可逆的改变,可能是由类淀粉体堆积相关的机制造成。 The evidence is accumulating that prion diseases are due to proteins which change their conformation irreversibly during an association reaction, perhaps by mechanisms related to amyloid accumulation.
- 主题A:鉴定蛋白感染素的病源与它的传染性
Topic A: Indefication of the prion agent and its transmissability.
- 主题B:单离的蛋白感染素的结构研究
Topic B: Structural characterization of the isolated prion protein.
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| 29 |
轻链淀粉样病变 Light Chain Amyloidosis |
一种称为多发性骨髓瘤的血癌癌症病患好发轻链生产过量的类淀粉堆积。 这凝集反应的某些部份可以在试管实验再现。 Cancer patients with a form of leukemia called multiple myeloma often accumulate amyloid deposits composed of the overproduced light chains. Some aspects of this aggregation reaction can be reproduced in vitro. |
| 30 |
纤维性囊肿的CFTR缺陷 The CFTR Defect in Cystic Fibrosis |
纤维性囊肿的病因是因为呼吸道的氯离子传送蛋白质有缺陷,近年的证据指出最常见的遗传形是因为蛋白质折叠缺陷。 Cystic fibrosis is due to a defect in the chloride transporter protein in the respiratory tract. Recent evidence indicates that the most common inherited form is due to a protein folding defect. |
| 31 |
肌萎缩性脊髓侧索硬化症(渐冻人症)的超氧化物歧化酶缺陷 Superoxide Dismutase Defect in ALS (Lou Gehrig's Disease) |
近年的证据指出肌萎缩性脊髓侧索硬化症与超氧化物歧化酶这个广泛分布的酵素有关,相关的氨基酸取代会影响此酶的折叠及稳定性而非代谢功能。 Recent evidence indicates that amylotrophic lateral sclerosis is associated with a defect in the function of the widely distributed protein Superoxide Dismutase. The associated amino acid substitution may affect folding or stability rather than metabolic function. |
| 32 |
家族性肺病的抗胰岛蛋白酶缺陷 The Anti-Trypsin Defect in Familial Lung Disease |
渐增的肺对烟与灰尘伤害的敏感性被认为与某些作用在肺的抗弹性蛋白的对偶基因有关,近年的证据显示主要的家族形是因为蛋白质折叠缺陷。 Increased susceptibility to lung damage from smoking and dusts is associated with certain alleles of the anti-elastase that functions in the lung. Recent evidence reveals that their major familial form is due to a defect in the folding of the protein. |
| 33 |
前白蛋白与类淀粉疾病 Trans-thyretin and Amyloid Disease |
一类稀少但被研究透彻的类淀粉疾病是因为前白蛋白这个视黄醇携带蛋白的沉积,试管内的折叠与展开反应的特色与病理状况相符。 A rare but well studied slass of amyloid diseases are due to deposition of the carrier protein trans-thyretin which is a retinol carrier protein. Features of the in vitro unfolding/ refolding reaction correlate with the conditions that yield pathology. |
| 34 |
抗癌蛋白质基因的突变 Mutations in Tumor Suppressor Proteins |
肿瘤的生成通常与一群控制DNA复制或细胞分裂的胞内蛋白的失能有关,有些证据指出p16锚蛋白的某些突变也是造成蛋白折叠缺陷。 Loss of function of a number of cellular proteins, which control DNA replication and cell division, is associated with tumor formation. There is some evidence for the p16 ankyrin proteins that some of these mutations may represent protein folding defects. |
| 35 |
蛋白质凝集与亨廷顿症 Protein Aggregation in Huntington's Disease |
与出亨廷顿症有关的多蛋白胶黏产物最近被鉴定出,它的凝集型被发现于细胞核。 The protein polyglutimate product associated with Huntington's disease has recently been identified. An aggregated form of it is found within the cell nucleus. |