Role of mutations and post-translational modifications in systemic AL amyloidosis studied by cryo-EM

Systemic AL amyloidosis is caused by misfolding of immunoglobulin light chains (LCs) but how post-translational modifications (PTMs) of LCs influence amyloid formation is not well understood. Here, the authors present the cryo-EM structure of an AL amyloid fibril derived from the heart tissue of a p...

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Autores principales:	Lynn Radamaker, Sara Karimi-Farsijani, Giada Andreotti, Julian Baur, Matthias Neumann, Sarah Schreiner, Natalie Berghaus, Raoul Motika, Christian Haupt, Paul Walther, Volker Schmidt, Stefanie Huhn, Ute Hegenbart, Stefan O. Schönland, Sebastian Wiese, Clarissa Read, Matthias Schmidt, Marcus Fändrich
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Science Q
Acceso en línea:	https://doaj.org/article/0c01463d3d2340dc9ac1ed41d176f4a7
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spelling	oai:doaj.org-article:0c01463d3d2340dc9ac1ed41d176f4a72021-11-08T11:06:17ZRole of mutations and post-translational modifications in systemic AL amyloidosis studied by cryo-EM10.1038/s41467-021-26553-92041-1723https://doaj.org/article/0c01463d3d2340dc9ac1ed41d176f4a72021-11-01T00:00:00Zhttps://doi.org/10.1038/s41467-021-26553-9https://doaj.org/toc/2041-1723Systemic AL amyloidosis is caused by misfolding of immunoglobulin light chains (LCs) but how post-translational modifications (PTMs) of LCs influence amyloid formation is not well understood. Here, the authors present the cryo-EM structure of an AL amyloid fibril derived from the heart tissue of a patient that is partially pyroglutamylated, N-glycosylated and contains an intramolecular disulfide bond. Based on their structure and biochemical experiments the authors conclude that the mutational changes, disulfide bond and glycosylation determine the fibril protein fold and that glycosylation protects the fibril core from proteolytic degradation.Lynn RadamakerSara Karimi-FarsijaniGiada AndreottiJulian BaurMatthias NeumannSarah SchreinerNatalie BerghausRaoul MotikaChristian HauptPaul WaltherVolker SchmidtStefanie HuhnUte HegenbartStefan O. SchönlandSebastian WieseClarissa ReadMatthias SchmidtMarcus FändrichNature PortfolioarticleScienceQENNature Communications, Vol 12, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Science Q
spellingShingle	Science Q Lynn Radamaker Sara Karimi-Farsijani Giada Andreotti Julian Baur Matthias Neumann Sarah Schreiner Natalie Berghaus Raoul Motika Christian Haupt Paul Walther Volker Schmidt Stefanie Huhn Ute Hegenbart Stefan O. Schönland Sebastian Wiese Clarissa Read Matthias Schmidt Marcus Fändrich Role of mutations and post-translational modifications in systemic AL amyloidosis studied by cryo-EM
description	Systemic AL amyloidosis is caused by misfolding of immunoglobulin light chains (LCs) but how post-translational modifications (PTMs) of LCs influence amyloid formation is not well understood. Here, the authors present the cryo-EM structure of an AL amyloid fibril derived from the heart tissue of a patient that is partially pyroglutamylated, N-glycosylated and contains an intramolecular disulfide bond. Based on their structure and biochemical experiments the authors conclude that the mutational changes, disulfide bond and glycosylation determine the fibril protein fold and that glycosylation protects the fibril core from proteolytic degradation.
format	article
author	Lynn Radamaker Sara Karimi-Farsijani Giada Andreotti Julian Baur Matthias Neumann Sarah Schreiner Natalie Berghaus Raoul Motika Christian Haupt Paul Walther Volker Schmidt Stefanie Huhn Ute Hegenbart Stefan O. Schönland Sebastian Wiese Clarissa Read Matthias Schmidt Marcus Fändrich
author_facet	Lynn Radamaker Sara Karimi-Farsijani Giada Andreotti Julian Baur Matthias Neumann Sarah Schreiner Natalie Berghaus Raoul Motika Christian Haupt Paul Walther Volker Schmidt Stefanie Huhn Ute Hegenbart Stefan O. Schönland Sebastian Wiese Clarissa Read Matthias Schmidt Marcus Fändrich
author_sort	Lynn Radamaker
title	Role of mutations and post-translational modifications in systemic AL amyloidosis studied by cryo-EM
title_short	Role of mutations and post-translational modifications in systemic AL amyloidosis studied by cryo-EM
title_full	Role of mutations and post-translational modifications in systemic AL amyloidosis studied by cryo-EM
title_fullStr	Role of mutations and post-translational modifications in systemic AL amyloidosis studied by cryo-EM
title_full_unstemmed	Role of mutations and post-translational modifications in systemic AL amyloidosis studied by cryo-EM
title_sort	role of mutations and post-translational modifications in systemic al amyloidosis studied by cryo-em
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0c01463d3d2340dc9ac1ed41d176f4a7
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Role of mutations and post-translational modifications in systemic AL amyloidosis studied by cryo-EM

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