Molecular chaperone activity of the 20S proteasome : Inhibitory activity of the substrate protein aggregation and unflodase activity

20S蛋白酶体的分子伴侣活性：底物蛋白聚集的抑制活性和解链酶活性

• 批准号: 13470026
• 负责人: KIDO Hiroshi
• 金额: $ 3.84万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470026/
• 关键词: Molecular chaperone; Proteasome; 19S Cap; Refolding; Aggregation of heat-denatured proteins; ATP; ADP; ATP-ADP exchange reaction; Hsp70; アンフォールディング; 活性中心

Cellular proteases and molecular chaperone proteins play important roles in the intracellular protein catabolism. Among the proteases, a multi-functional 20S proteasome, which is composed of 28 low molecular mass subunits arranged in a stack of four rings, each containing seven different α- and β-subunits, plays a central role in the degradation of unfolded and/or misfolded proteins in the cytosol in cooperation with molecular chaperones. We found that the C5 in theβ-type and the C8 in theα-type subunits of the 20S proteasome reveal the activities of ATP hydrolysis and ADP-ATP exchange, which are similar to the activities of molecular chaperone and essential to the association and dissociation of substrate proteins and peptides. Furthermore, 20S proteasome reveals a chaperone-like activity, an inhibition of the aggregation of heat-denatured proteins, in an ATP-independent manner and degradation of unfolded protein in an ATP-dependent manner. These results suggest the activities of ATP hydrolysis and ATP-ADP exchange of the 20S proteasome play a role in translocation of unfolded and/or misfolded proteins into the catalytic cavity of the inside of ring-shaped 20S proteasome but not play a role in inhibition of the aggregation of heat-denatured proteins.

细胞蛋白酶和分子伴侣蛋白在细胞内蛋白质分解代谢中发挥重要作用。在蛋白酶中，多功能20S蛋白酶体由28个低分子量亚基组成，排列成四个环，每个亚基包含七个不同的α和β亚基，与分子伴侣配合，在胞质溶胶中未折叠和/或错误折叠蛋白质的降解中发挥核心作用。我们发现20S蛋白酶体β型亚基中的C5和α型亚基中的C8具有ATP水解和ADP-ATP交换活性，这与分子伴侣的活性相似，对于底物蛋白和肽的结合和解离至关重要。此外，20S蛋白酶体显示出类似分子伴侣的活性，以不依赖于ATP的方式抑制热变性蛋白质的聚集，并以依赖于ATP的方式降解未折叠的蛋白质。这些结果表明20S蛋白酶体的ATP水解和ATP-ADP交换活性在未折叠和/或错误折叠的蛋白质易位到环形20S蛋白酶体内部的催化空腔中发挥作用，但在抑制热变性蛋白质的聚集中没有发挥作用。

项目成果

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Yano, M.: "Chaperon activities of the 26S and 20S proteasome"Current Protein and Peptide Science. (in press). (2003)

Yano, M.：“26S 和 20S 蛋白酶体的伴侣活性”当前蛋白质和肽科学。