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-Structure paper
タイトル | Structural basis for transthyretin amyloid formation in vitreous body of the eye. |
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ジャーナル・号・ページ | Nat Commun, Vol. 12, Issue 1, Page 7141, Year 2021 |
掲載日 | 2021年12月8日 |
著者 | Irina Iakovleva / Michael Hall / Melanie Oelker / Linda Sandblad / Intissar Anan / A Elisabeth Sauer-Eriksson / |
PubMed 要旨 | Amyloid transthyretin (ATTR) amyloidosis is characterized by the abnormal accumulation of ATTR fibrils in multiple organs. However, the structure of ATTR fibrils from the eye is poorly understood. ...Amyloid transthyretin (ATTR) amyloidosis is characterized by the abnormal accumulation of ATTR fibrils in multiple organs. However, the structure of ATTR fibrils from the eye is poorly understood. Here, we used cryo-EM to structurally characterize vitreous body ATTR fibrils. These structures were distinct from previously characterized heart fibrils, even though both have the same mutation and type A pathology. Differences were observed at several structural levels: in both the number and arrangement of protofilaments, and the conformation of the protein fibril in each layer of protofilaments. Thus, our results show that ATTR protein structure and its assembly into protofilaments in the type A fibrils can vary between patients carrying the same mutation. By analyzing and matching the interfaces between the amino acids in the ATTR fibril with those in the natively folded TTR, we are able to propose a mechanism for the structural conversion of TTR into a fibrillar form. |
リンク | Nat Commun / PubMed:34880242 / PubMed Central |
手法 | EM (らせん対称) |
解像度 | 3.22 Å |
構造データ | EMDB-12794, PDB-7ob4: |
由来 |
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キーワード | PROTEIN FIBRIL / AMYLOID FIBRIL / TRANSTHYRETIN / MISFOLDING / ATTR AMYLOIDOSIS / V30M VARIANT / EX VIVO / VITREOUS BODY |