6533b7d1fe1ef96bd125d7b0
RESEARCH PRODUCT
High-yield Production of Amyloid-β Peptide Enabled by a Customized Spider Silk Domain
Michael LandrehNina KronqvistGefei ChenAxel AbeleinKristīne KitokaMédoune SarrJens PahnkeKristaps JaudzemsRihards AleksisHenrik BiverstålAnna RisingAnna RisingJan JohanssonFilips OleskovsKerstin Nordlingsubject
Models Molecular0301 basic medicineProtein domainBiophysicslcsh:MedicinePeptideBiosynthesis010402 general chemistryBiochemistry01 natural sciencesArticlelaw.invention03 medical and health sciencesProtein DomainslawAnimalsSpider silkAmino Acid SequenceNeurodegenerationlcsh:SciencePeptide sequencechemistry.chemical_classificationAmyloid beta-PeptidesMultidisciplinarybiologySpidroinlcsh:RNeurodegenerative diseasesNephila clavipesProteinsbiology.organism_classification0104 chemical sciences030104 developmental biologyBiochemistrychemistryYield (chemistry)Recombinant DNAlcsh:QPeptidesFibroinsdescription
AbstractDuring 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2020-01-14 | Scientific Reports |