β2-微球蛋白淀粉样生成早期天然样中间态结构。
Structure of an early native-like intermediate of β2-microglobulin amyloidogenesis.
机构信息
Structural Biology Research Centre, VIB, Pleinlaan 2, 1050, Brussel, Belgium; Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussel, Belgium.
出版信息
Protein Sci. 2013 Oct;22(10):1349-57. doi: 10.1002/pro.2321. Epub 2013 Aug 20.
Abstract
To investigate early intermediates of β2-microglobulin (β2m) amyloidogenesis, we solved the structure of β2m containing the amyloidogenic Pro32Gly mutation by X-ray crystallography. One nanobody (Nb24) that efficiently blocks fibril elongation was used as a chaperone to co-crystallize the Pro32Gly β2m monomer under physiological conditions. The complex of P32G β2m with Nb24 reveals a trans peptide bond at position 32 of this amyloidogenic variant, whereas Pro32 adopts the cis conformation in the wild-type monomer, indicating that the cis to trans isomerization at Pro32 plays a critical role in the early onset of β2m amyloid formation.
摘要
为了研究β2-微球蛋白（β2m）淀粉样变的早期中间产物，我们通过 X 射线晶体学解析了含有淀粉样变 Pro32Gly 突变的β2m 结构。一种能够有效阻止纤维延伸的纳米抗体（Nb24）被用作分子伴侣，在生理条件下共结晶 Pro32Gly β2m 单体。P32G β2m 与 Nb24 的复合物揭示了该淀粉样变变体 32 位的反式肽键，而野生型单体中的 Pro32 采用顺式构象，表明 Pro32 的顺式到反式异构化在β2m 淀粉样形成的早期发生中起着关键作用。
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