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| Verfasst von: | Kazman, Pamina [VerfasserIn]  |
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| | Vielberg, Marie-Theres [VerfasserIn] |
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| | Pulido Cendales, María Daniela [VerfasserIn] |
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| | Hunziger, Lioba [VerfasserIn] |
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| | Weber, Benedikt [VerfasserIn] |
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| | Hegenbart, Ute [VerfasserIn] |
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| | Zacharias, Martin [VerfasserIn] |
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| | Köhler, Rolf [VerfasserIn] |
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| | Schönland, Stefan [VerfasserIn] |
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| | Groll, Michael [VerfasserIn] |
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| | Buchner, Johannes [VerfasserIn] |
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| Titel: | Fatal amyloid formation in a patient’s antibody light chain is caused by a single point mutation |
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| Verf.angabe: | Pamina Kazman, Marie-Theres Vielberg, María Daniela Pulido Cendales, Lioba Hunziger, Benedikt Weber, Ute Hegenbart, Martin Zacharias, Rolf Köhler, Stefan Schönland, Michael Groll, Johannes Buchner |
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| E-Jahr: | 2020 |
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| Jahr: | 10 March 2020 |
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| Fussnoten: | Gesehen am 11.03.2020 |
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| Titel Quelle: | Enthalten in: eLife |
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| Ort Quelle: | Cambridge : eLife Sciences Publications, 2012 |
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| Jahr Quelle: | 2020 |
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| Band/Heft Quelle: | 9(2020) Artikel-Nummer e52300, 23 Seiten |
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| ISSN Quelle: | 2050-084X |
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| Abstract: | In systemic light chain amyloidosis, an overexpressed antibody light chain (LC) forms fibrils which deposit in organs and cause their failure. While it is well-established that mutations in the LC’s VL domain are important prerequisites, the mechanisms which render a patient LC amyloidogenic are ill-defined. In this study, we performed an in-depth analysis of the factors and mutations responsible for the pathogenic transformation of a patient-derived λ LC, by recombinantly expressing variants in E. coli. We show that proteolytic cleavage of the patient LC resulting in an isolated VL domain is essential for fibril formation. Out of 11 mutations in the patient VL, only one, a leucine to valine mutation, is responsible for fibril formation. It disrupts a hydrophobic network rendering the C-terminal segment of VL more dynamic and decreasing domain stability. Thus, the combination of proteolytic cleavage and the destabilizing mutation trigger conformational changes that turn the LC pathogenic. |
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| DOI: | doi:10.7554/eLife.52300 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.7554/eLife.52300 |
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| | DOI: https://doi.org/10.7554/eLife.52300 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | AL amyloidosis |
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| | antibody light chain |
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| | hydrophobic interactions |
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| | protein dynamics |
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| | protein stability |
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| K10plus-PPN: | 1692235052 |
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| Verknüpfungen: | → Zeitschrift |
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Fatal amyloid formation in a patient’s antibody light chain is caused by a single point mutation / Kazman, Pamina [VerfasserIn]; 10 March 2020 (Online-Ressource)
