AA amyloid fibrils from diseased tissue are structurally different from in vitro formed SAA fibrils.
AA amyloid fibrils from diseased tissue are structurally different from in vitro formed SAA fibrils.
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DOI：
10.1038/s41467-021-21129-z
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发表时间：
2021-02-12
影响因子：
16.6
通讯作者：
Fändrich M
中科院分区：
文献类型：
--
作者：
Bansal A;Schmidt M;Rennegarbe M;Haupt C;Liberta F;Stecher S;Puscalau-Girtu I;Biedermann A;Fändrich M
系统性AA淀粉样变性是一种世界性的蛋白质错误折叠疾病。它起源于血清淀粉样蛋白A（SAA）蛋白形成淀粉样纤维。使用冷冻电子显微镜，我们在这里表明，从AA淀粉样变性小鼠中纯化的淀粉样纤维在结构上不同于从重组SAA蛋白在体外形成的纤维。离体淀粉样蛋白原纤维由原纤维蛋白组成，所述原纤维蛋白在其有序部分内含有更多残基并且具有比体外原纤维蛋白更高的β-折叠含量。它们也比它们在体外形成的对应物更耐蛋白水解。这些数据表明，致病性淀粉样蛋白原纤维可能源于蛋白水解选择，允许特定的原纤维形态增殖，并对周围组织造成损伤。系统性AA淀粉样变性是由血清淀粉样蛋白A（SAA）形成淀粉样纤维引起的蛋白质错误折叠疾病。在这里，作者提出了从小鼠组织中分离的AA淀粉样蛋白原纤维和体外形成的原纤维的冷冻电镜结构，它们的结构不同，并且他们还表明离体原纤维比体外原纤维更耐蛋白水解，并提出致病性淀粉样蛋白原纤维可能起源于蛋白水解选择。
Systemic AA amyloidosis is a world-wide occurring protein misfolding disease of humans and animals. It arises from the formation of amyloid fibrils from serum amyloid A (SAA) protein. Using cryo electron microscopy we here show that amyloid fibrils which were purified from AA amyloidotic mice are structurally different from fibrils formed from recombinant SAA protein in vitro. Ex vivo amyloid fibrils consist of fibril proteins that contain more residues within their ordered parts and possess a higher β-sheet content than in vitro fibril proteins. They are also more resistant to proteolysis than their in vitro formed counterparts. These data suggest that pathogenic amyloid fibrils may originate from proteolytic selection, allowing specific fibril morphologies to proliferate and to cause damage to the surrounding tissue. Systemic AA amyloidosis is a protein misfolding disease caused by the formation of amyloid fibrils from serum amyloid A (SAA) protein. Here, the authors present the cryo-EM structures of AA amyloid fibrils isolated from mouse tissue and in vitro formed fibrils, which differ in their structures and they also show that the ex vivo fibrils are more resistant to proteolysis than the in vitro fibrils and propose that pathogenic amyloid fibrils might originate from proteolytic selection.
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影响因子：
3
作者：
Kremer, JR;Mastronarde, DN;McIntosh, JR
通讯作者：
McIntosh, JR
影响因子：
3
作者：
He, Shaoda;Scheres, Sjors H. W.
通讯作者：
Scheres, Sjors H. W.
DOI：
10.1107/s2059798319011471
发表时间：
2019-10-01
影响因子：
2.2
作者：
Liebschner, Dorothee;Afonine, Pavel V.;Adams, Paul D.
通讯作者：
Adams, Paul D.
影响因子：
64.5
作者：
Eisenberg D;Jucker M
通讯作者：
Jucker M
DOI：
10.1080/13506129.2019.1628015
发表时间：
2019-06-24
影响因子：
5.5
作者：
Liberta, Falk;Rennegarbe, Matthies;Fandrich, Marcus
通讯作者：
Fandrich, Marcus