High-yield Production of Amyloid-β Peptide Enabled by a Customized Spider Silk Domain

Axel Abelein; Gefei Chen; Kristīne Kitoka; Rihards Aleksis; Filips Oleskovs; Médoune Sarr; Michael Landreh; Jens Pahnke; Kerstin Nordling; Nina Kronqvist; Kristaps Jaudzems; Anna Rising; Jan Johansson; Henrik Biverstål

doi:10.1038/s41598-019-57143-x

High-yield Production of Amyloid-β Peptide Enabled by a Customized Spider Silk Domain

Axel Abelein, Gefei Chen, Kristīne Kitoka, Rihards Aleksis, Filips Oleskovs, Médoune Sarr, Michael Landreh, Jens Pahnke, Kerstin Nordling, Nina Kronqvist, Kristaps Jaudzems, Anna Rising, Jan Johansson, Henrik Biverstål^*

^*Korrespondierende/r Autor/-in für diese Arbeit

Lübecker Institut für Experimentelle Dermatologie (LIED)

54 Zitate (Scopus)

Abstract

During storage in the silk gland, the N-terminal domain (NT) of spider silk proteins (spidroins) keeps the aggregation-prone repetitive region in solution at extreme concentrations. We observe that NTs from different spidroins have co-evolved with their respective repeat region, and now use an NT that is distantly related to previously used NTs, for efficient recombinant production of the amyloid-β peptide (Aβ) implicated in Alzheimer’s disease. A designed variant of NT from Nephila clavipes flagelliform spidroin, which in nature allows production and storage of β-hairpin repeat segments, gives exceptionally high yields of different human Aβ variants as a solubility tag. This tool enables efficient production of target peptides also in minimal medium and gives up to 10 times more isotope-labeled monomeric Aβ peptides per liter bacterial culture than previously reported.

Originalsprache	Englisch
Aufsatznummer	235
Zeitschrift	Scientific Reports
Jahrgang	10
Ausgabenummer	1
ISSN	2045-2322
DOIs	https://doi.org/10.1038/s41598-019-57143-x
Publikationsstatus	Veröffentlicht - 01.12.2020

Fördermittel

This study was supported by the Magnus Bergvall foundation (A.A., H.B.), FLPP/Latvia lzp-2018/1-0275 project support (H.B., J.P.), Swedish Research Council (A.R., J.J.), Center for Innovative Medicine (CIMED) (A.R. J.J.), FORMAS (A.R.), Vinnova (J.J.), Olle Engkvists Foundation (G.C.), Swedish Alzheimer foundation (G.C.), Åhlen Foundation (A.A., G.C., H.B.), Stiftelsen för Gamla Tjänarinnor (A.A., H.B., G.C.), P. & A. Hedlunds Stiftelse (G.C.), Instruct R&D pilot project grant APPID 272 (A.A.), Loo and Hans Osterman Foundation (A.A., G.C.), Geriatric Diseases Foundation at Karolinska Institutet (A.A., G.C.), Norsk forskningsrådet 251290, 260786 (J.P.), JPco-fuND/EU PROP-AD 643417/Horizon 2020/EC 643417 (H.B., J.P.).

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10.1038/s41598-019-57143-x

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title = "High-yield Production of Amyloid-β Peptide Enabled by a Customized Spider Silk Domain",

abstract = "During storage in the silk gland, the N-terminal domain (NT) of spider silk proteins (spidroins) keeps the aggregation-prone repetitive region in solution at extreme concentrations. We observe that NTs from different spidroins have co-evolved with their respective repeat region, and now use an NT that is distantly related to previously used NTs, for efficient recombinant production of the amyloid-β peptide (Aβ) implicated in Alzheimer{\textquoteright}s disease. A designed variant of NT from Nephila clavipes flagelliform spidroin, which in nature allows production and storage of β-hairpin repeat segments, gives exceptionally high yields of different human Aβ variants as a solubility tag. This tool enables efficient production of target peptides also in minimal medium and gives up to 10 times more isotope-labeled monomeric Aβ peptides per liter bacterial culture than previously reported.",

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AU - Abelein, Axel

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AU - Aleksis, Rihards

AU - Oleskovs, Filips

AU - Sarr, Médoune

AU - Landreh, Michael

AU - Pahnke, Jens

AU - Nordling, Kerstin

AU - Kronqvist, Nina

AU - Jaudzems, Kristaps

AU - Rising, Anna

AU - Johansson, Jan

AU - Biverstål, Henrik

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High-yield Production of Amyloid-β Peptide Enabled by a Customized Spider Silk Domain

Abstract

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UN SDGs

Strategische Forschungsbereiche und Zentren

Dokumente

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