Protein folding and localization in the cell

该项目的最终目的是了解新合成的蛋白质在获得生物功能结构和在细胞内定位的过程中遵循的原理和途径。这项合作研究的更具体目标是促进积极参与这一快速发展领域的研究人员之间的信息交流和合作。以下是对结果的简要总结。后藤获得的结果表明，蛋白质的“熔融球状”结构是在生理条件下发生的。Yura在大肠杆菌热休克反应中发现了一种翻译调控，并确定了大肠杆菌热休克蛋白的几种生理功能。Kagawa从一种嗜热细菌中发现了热休克基因和蛋白质。Yahara发现了Hsp90在核作用受体-细胞骨架相互作用以及Hsp90-酪蛋白激酶II复合物中的作用。Kohno发现了人类XPAC同源物携带的核靶向信号。Mizushima从大肠杆菌的SecA， SecY和SecE中发现了更多的蛋白质易位，并解剖了蛋白质分泌的信号序列。Ito发现了对催化和Sec复合物形成很重要的SecY结构域，以及在二硫键形成中起作用的质周折叠因子（PpfA）。Amaya发现了SRP亚基54的酵母同源物，并表明它参与蛋白质转运到内质网。Sakaguchi指出，电荷分布和疏水性是蛋白质插入内质网膜的主要决定因素。Endo构建了一个系统来监测线粒体前体蛋白在易位过程中的构象变化。osumii发现了一个可切割的n端信号，用于将3-酮酰基辅酶a硫醇酶靶向过氧化物酶体。Mizunaga克隆了酵母蛋白二硫异构酶基因并对其进行了测序，结果表明该基因对酵母的生存至关重要。Yoshimori表明，一些内质网驻留蛋白可以在大鼠外分泌胰腺细胞中分泌。Hirayoshi确定了Hsp47基因，并提出Hsp47是胶原特异性伴侣蛋白。Nakano表明，酵母中SarIP的GTPase活性是内质网向高尔基蛋白转运所必需的，这可能是在囊泡形成之后的一个步骤。Tokunaga纯化并鉴定了酵母BiP。少

The ultimate aim of this project is to understand the principles and the pathway that newly synthesized proteins of follow in their process of acquisition of biologically functional structure and localization within the cell. More specific objective of this Cooperative Research is to stimulate information exchange and collaborations among researchers actively involved in this rapidly developing field. Following are brief summaries of the results.Goto obtained results that suggest"molten globule"structure of proteins occurs under physionlogical conditions. Yura discovered a translational regulation in the heat shock response of E. coli and identified several physiological functions of E. coli Hsps. Kagawa identified heat shok genes and proteins from a thermophilic bacterium. Yahara discovered Hsp90's role in nuclear-acting receptor-cytoskeleton interactions as well as Hsp90-casein kinase II complex. Kohno identified nuclear targeting signal carried on huma XPAC homolog. Mizushima recost … More ituted protein translocation from SecA, SecY and SecE of E. coli and dissected signal sequences for protein secretion. Ito identified SecY's domains important for calalysis and Sec complex formation, as well as a periplasmic folding factor (PpfA) acting at the disulfied bond formation. Amaya identified a yeast homolog of SRP subunit 54 and showed that it is involved in protein translocation into ER. Sakaguchi showed that charge distribution and hydrophobicity are major determinants of the orientation in protein insertion into ER membrane. Endo constructed a system to monitor conformational changes of a mitochaondrial precursor protein during translocation. Osumiidentified a cleavable N-terminal signal for targeting of 3-ketoacyl-CoA thiolase to peroxisomes. Mizunaga cloned and sequenced the yeast protein disulfide isomerase gene and showed that it is essential for viability. Yoshimori showed that some ER resident proteins can be secreted in rat exocrine pancreative cells. Hirayoshi determined the Hsp47 gene and proposed that Hsp47 is a collagen-specific chaperone. Nakano showed that the GTPase activity of SarIP in yeast is required for ER to Golgiprotein transport probably at a step subsequent to vesicle formation. Tokunaga purified and characterized yeast BiP. Less