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^*

^*Corresponding author for this work

Institute of Experimental Dermatology

1 Citation (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.

Original language	English
Article number	235
Journal	Scientific Reports
Volume	10
Issue number	1
ISSN	2045-2322
DOIs	https://doi.org/10.1038/s41598-019-57143-x
Publication status	Published - 01.12.2020

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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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

AU - Chen, Gefei

AU - Kitoka, Kristīne

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

PY - 2020/12/1

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AB - 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.

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

Abstract

Research Areas and Centers

UN SDGs

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