The group II chaperonin Mm-Cpn binds and refolds human γD crystallin.
The group II chaperonin Mm-Cpn binds and refolds human γD crystallin.
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II 组伴侣蛋白 Mm-Cpn 结合并重新折叠人 γD 晶状体蛋白。
DOI：
10.1002/pro.531
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
King,JonathanA
中科院分区：
文献类型：
--
作者：
Knee,KellyM;Goulet,DanielR;Zhang,Junjie;Chen,Bo;Chiu,Wah;King,JonathanA
伴侣蛋白有助于新生和错误折叠的蛋白质的折叠，尽管伴侣蛋白内腔内的折叠机制仍然知之甚少。来自马拉巴氏甲烷球菌的原始伴侣蛋白Mm-Cpn与其他II组伴侣蛋白（包括肌动蛋白和微管蛋白折叠所需的真核TRiC/CCT）共享八重双桶结构。然而，Mm-Cpn由单一种类的亚基组成，类似于I组伴侣蛋白GroEL，而不是TRiC/CCT所需的八种亚基种类。β折叠的特征已被鉴定为II组伴侣蛋白识别的位点。晶状体蛋白是脊椎动物眼透镜的主要成分，是具有两个同源希腊关键结构域的β折叠蛋白。在体外再折叠过程中，部分折叠的中间体被填充，并且在生产性折叠和路径外聚集之间进行划分。我们在此报告，在生理浓度的ATP存在下，Mm-Cpn通过结合部分折叠的中间体抑制H γ D-Crys的聚集。该复合物足够稳定，可以通过尺寸排阻色谱法回收。在ATP存在下，Mm-Cpn促进H γ D-Crys中间体重折叠至天然状态。Mm-Cpn结合和重折叠人β折叠蛋白的能力表明，Mm-Cpn可用作TRiC/CCT底物识别机制的简化模型。
Chaperonins assist in the folding of nascent and misfolded proteins, though the mechanism of folding within the lumen of the chaperonin remains poorly understood. The archeal chaperonin fromMethanococcus marapaludis, Mm‐Cpn, shares the eightfold double barrel structure with other group II chaperonins, including the eukaryotic TRiC/CCT, required for actin and tubulin folding. However, Mm‐Cpn is composed of a single species subunit, similar to group I chaperonin GroEL, rather than the eight subunit species needed for TRiC/CCT. Features of the β‐sheet fold have been identified as sites of recognition by group II chaperonins. The crystallins, the major components of the vertebrate eye lens, are β‐sheet proteins with two homologous Greek key domains. During refoldingin vitroa partially folded intermediate is populated, and partitions between productive folding and off‐pathway aggregation. We report here that in the presence of physiological concentrations of ATP, Mm‐Cpn suppressed the aggregation of HγD‐Crys by binding the partially folded intermediate. The complex was sufficiently stable to permit recovery by size exclusion chromatography. In the presence of ATP, Mm‐Cpn promoted the refolding of the HγD‐Crys intermediates to the native state. The ability of Mm‐Cpn to bind and refold a human β‐sheet protein suggests that Mm‐Cpn may be useful as a simplified model for the substrate recognition mechanism of TRiC/CCT.