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-Structure paper
タイトル | Cryo-EM structure of a light chain-derived amyloid fibril from a patient with systemic AL amyloidosis. |
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ジャーナル・号・ページ | Nat Commun, Vol. 10, Issue 1, Page 1103, Year 2019 |
掲載日 | 2019年3月20日 |
著者 | Lynn Radamaker / Yin-Hsi Lin / Karthikeyan Annamalai / Stefanie Huhn / Ute Hegenbart / Stefan O Schönland / Günter Fritz / Matthias Schmidt / Marcus Fändrich / |
PubMed 要旨 | Amyloid fibrils derived from antibody light chains are key pathogenic agents in systemic AL amyloidosis. They can be deposited in multiple organs but cardiac amyloid is the major risk factor of ...Amyloid fibrils derived from antibody light chains are key pathogenic agents in systemic AL amyloidosis. They can be deposited in multiple organs but cardiac amyloid is the major risk factor of mortality. Here we report the structure of a λ1 AL amyloid fibril from an explanted human heart at a resolution of 3.3 Å which we determined using cryo-electron microscopy. The fibril core consists of a 91-residue segment presenting an all-beta fold with ten mutagenic changes compared to the germ line. The conformation differs substantially from natively folded light chains: a rotational switch around the intramolecular disulphide bond being the crucial structural rearrangement underlying fibril formation. Our structure provides insight into the mechanism of protein misfolding and the role of patient-specific mutations in pathogenicity. |
リンク | Nat Commun / PubMed:30894526 / PubMed Central |
手法 | EM (らせん対称) |
解像度 | 3.3 Å |
構造データ | |
由来 |
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キーワード | PROTEIN FIBRIL / amyloid fibril / beta sheet / antibody / heart |