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Research article2023Peer reviewedOpen access

Liquid-Liquid Phase Separation Primes Spider Silk Proteins for Fiber Formation via a Conditional Sticker Domain

Leppert, Axel; Chen, Gefei; Lama, Dilraj; Sahin, Cagla; Railaite, Vaida; Shilkova, Olga; Arndt, Tina; Marklund, Erik G.; Lane, David P.; Rising, Anna; Landreh, Michael


Many protein condensates can convert to fibrillar aggregates, but the underlying mechanisms are unclear. Liquid-liquid phase separation (LLPS) of spider silk proteins, spidroins, suggests a regulatory switch between both states. Here, we combine microscopy and native mass spectrometry to investigate the influence of protein sequence, ions, and regulatory domains on spidroin LLPS. We find that salting out-effects drive LLPS via low-affinity stickers in the repeat domains. Interestingly, conditions that enable LLPS simultaneously cause dissociation of the dimeric C-terminal domain (CTD), priming it for aggregation. Since the CTD enhances LLPS of spidroins but is also required for their conversion into amyloid-like fibers, we expand the stickers and spacers-model of phase separation with the concept of folded domains as conditional stickers that represent regulatory units.


Phase separation; native mass spectrometry; stickers and spacers-model; functional amyloid

Published in

Nano Letters
2023, Volume: 23, number: 12, pages: 5836-5841 Publisher: AMER CHEMICAL SOC

    UKÄ Subject classification

    Biochemistry and Molecular Biology

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