Structural polymorphism of amyloid fibrils in ATTR amyloidosis revealed by cryo-electron microscopy.
Structural polymorphism of amyloid fibrils in ATTR amyloidosis revealed by cryo-electron microscopy.
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DOI：
10.1038/s41467-024-44820-3
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发表时间：
2024-01-17
影响因子：
16.6
通讯作者：
Saelices L
中科院分区：
文献类型：
--
作者：
Nguyen BA;Singh V;Afrin S;Yakubovska A;Wang L;Ahmed Y;Pedretti R;Fernandez-Ramirez MDC;Singh P;Pękała M;Cabrera Hernandez LO;Kumar S;Lemoff A;Gonzalez-Prieto R;Sawaya MR;Eisenberg DS;Benson MD;Saelices L
ATTR淀粉样变性是由甲状腺素运载蛋白以淀粉样纤维的形式沉积在身体的几乎每个器官（包括心脏）中引起的。这种系统性沉积导致表型变异，尚未在分子上解释。在脑淀粉样蛋白条件下，以前的研究表明临床表型和淀粉样蛋白原纤维的分子结构之间的关联。在这里，我们调查是否有这样的关联在ATTRv淀粉样变性患者携带突变I84 S。使用冷冻电子显微镜，我们确定了从三个ATTR淀粉样变性患者携带ATTRv-I84 S突变，与一致的临床表型相关提取的心脏原纤维的结构。我们发现，在每个ATTRv-I84 S患者中，心脏原纤维表现出不同的局部构象，并且这些变化可以在同一原纤维内共存。我们的发现提示一种淀粉样疾病可能与全身性淀粉样变性中的多种纤维结构有关，需要进一步研究。在这项工作中，作者报道了冷冻电镜成像揭示了具有相同基因突变I84 S的ATTR患者淀粉样纤维结构的多样性。进一步的研究是必要的，以掌握在ATTR淀粉样变性病理学的影响。
ATTR amyloidosis is caused by the deposition of transthyretin in the form of amyloid fibrils in virtually every organ of the body, including the heart. This systemic deposition leads to a phenotypic variability that has not been molecularly explained yet. In brain amyloid conditions, previous studies suggest an association between clinical phenotype and the molecular structures of their amyloid fibrils. Here we investigate whether there is such an association in ATTRv amyloidosis patients carrying the mutation I84S. Using cryo-electron microscopy, we determined the structures of cardiac fibrils extracted from three ATTR amyloidosis patients carrying the ATTRv-I84S mutation, associated with a consistent clinical phenotype. We found that in each ATTRv-I84S patient, the cardiac fibrils exhibited different local conformations, and these variations can co-exist within the same fibril. Our finding suggests that one amyloid disease may associate with multiple fibril structures in systemic amyloidoses, calling for further studies. In this work, the authors report Cryo-EM imaging revealing diversity in amyloid fibril structures among ATTR patients with the same genetic mutation I84S. Further study is warranted to grasp the implications in ATTR amyloidosis pathology.
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DOI：
10.1007/s00109-010-0695-1
发表时间：
2011-02
期刊：
Journal of molecular medicine (Berlin, Germany)
影响因子：
--
作者：
Ihse E;Suhr OB;Hellman U;Westermark P
通讯作者：
Westermark P
影响因子：
16.8
作者：
Cao, Qin;Boyer, David R.;Sawaya, Michael R.;Abskharon, Romany;Saelices, Lorena;Nguyen, Binh A.;Lu, Jiahui;Murray, Kevin A.;Kandeel, Fouad;Eisenberg, David S.
通讯作者：
Eisenberg, David S.
影响因子：
64.8
作者：
Arseni D;Hasegawa M;Murzin AG;Kametani F;Arai M;Yoshida M;Ryskeldi-Falcon B
通讯作者：
Ryskeldi-Falcon B
影响因子：
15.9
作者：
DWULET, FE;BENSON, MD
通讯作者：
BENSON, MD
影响因子：
2.2
作者：
Chen, Shaoxia;McMullan, Greg;Faruqi, Abdul R.;Murshudov, Garib N.;Short, Judith M.;Scheres, Sjors H. W.;Henderson, Richard
通讯作者：
Henderson, Richard