Sequence-specific Recognition of Collagen Triple Helices by the Collagen-specific Molecular Chaperone HSP47*
Sequence-specific Recognition of Collagen Triple Helices by the Collagen-specific Molecular Chaperone HSP47*
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胶原蛋白特异性分子伴侣 HSP47* 对胶原蛋白三螺旋的序列特异性识别
DOI：
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发表时间：
2002
影响因子：
4.8
通讯作者：
N. Bulleid
中科院分区：
文献类型：
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作者：
M. Tasab;Lynsey Jenkinson;N. Bulleid
HSP47 是一种分子伴侣，在原胶原的组装和运输过程中发挥着未知的作用。我们之前的研究表明，与大多数伴侣不同，HSP47 与正确折叠的底物相互作用。我们认为 HSP47 可以稳定正确折叠的胶原蛋白螺旋免受热变性，或者在其从内质网转运之前防止横向聚集。在这项研究中，我们通过表达具有不同热稳定性的前胶原分子并分析它们在内质网内与 HSP47 相互作用的能力，探讨了三螺旋稳定性在 HSP47 与前胶原结合中的作用。我们的结果表明，HSP47 与热稳定性前胶原分子相互作用，表明螺旋稳定不是 HSP47 的主要功能，并且 HSP47 与前胶原的相互作用取决于三螺旋结构域内至少存在一个 Gly-X-Arg 三联体。有趣的是，即使在没有脯氨酸羟基化的情况下，含有高比例稳定三联体的前胶原链也会形成三螺旋并与 HSP47 相互作用，这表明识别并不依赖于这种修饰。我们的结果支持这样的观点：HSP47 通过阻止原胶原链的横向聚集而在分泌途径的早期发挥作用。
HSP47 is a molecular chaperone that plays an unknown role during the assembly and transport of procollagen. Our previous studies showed that, unlike most chaperones, HSP47 interacts with a correctly folded substrate. We suggested that HSP47 either stabilizes the correctly folded collagen helix from heat denaturation or prevents lateral aggregation prior to its transport from the endoplasmic reticulum. In this study we have addressed the role of triple helix stability in the binding of HSP47 to procollagen by expressing procollagen molecules with differing thermal stabilities and analyzing their ability to interact with HSP47 within the endoplasmic reticulum. Our results show that HSP47 interacts with thermostable procollagen molecules, suggesting that helix stabilization is not the primary function of HSP47 and that the interaction of HSP47 with procollagen depends upon the presence of a minimum of one Gly-X-Arg triplet within the triple helical domain. Interestingly, procollagen chains containing high proportions of stabilizing triplets formed triple helices and interacted with HSP47 even in the absence of proline hydroxylation, demonstrating that recognition does not depend upon this modification. Our results support the view that HSP47 functions early in the secretory pathway by preventing the lateral aggregation of procollagen chains.
影响因子：
3
作者：
Ramshaw, JAM;Shah, NK;Brodsky, B
通讯作者：
Brodsky, B