Georg Meisl

Jan 12, 2025 | nature.com | Yiying Li |Georg Meisl

AbstractNucleoside triphosphate (NTP)-dependent protein assemblies such as microtubules and actin filaments have inspired the development of diverse chemically fueled molecular machines and active materials but their functional sophistication has yet to be matched by design.

Oct 11, 2024 | pubs.rsc.org | Kalyani Sanagavarapu |Georg Meisl |Katja Bernfur |Veronica Lattanzi

Serine phosphorylation mimics of Aβ form distinct, non-cross-seeding fibril morphs The self-assembly of amyloid-β peptide (Aβ) into fibrils and oligomers is linked to Alzheimer’s disease (AD). Fibrillar aggregates in AD patient’s brains contain several post-translational modifications, including phosphorylation at positions 8 and 26. These play a key role in modifying the aggregation propensity of Aβ, yet how they affect the mechanism of aggregation is only poorly understood.

Aug 17, 2024 | nature.com | Catherine Xu |Georg Meisl |Ewa Andrzejewska |Georg Krainer |Irina Edu |Michele Vendruscolo | +1 more

AbstractOligomeric species arising during the aggregation of α-synuclein are implicated as a major source of toxicity in Parkinson’s disease, and thus a major potential drug target. However, both their mechanism of formation and role in aggregation are largely unresolved. Here we show that, at physiological pH and in the absence of lipid membranes, α-synuclein aggregates form by secondary nucleation, rather than simple primary nucleation, and that this process is enhanced by agitation.

May 10, 2024 | pubs.rsc.org | Jiapeng Wei |Lensfield Road |Georg Meisl |Alexander J. Dear

Kinetic models reveal the interplay of protein production and aggregation† Protein aggregation is a key process in the development of many neurodegenerative disorders, including dementias such as Alzheimer's disease.

Mar 18, 2024 | nature.com | Danny D. Sahtoe |Ewa Andrzejewska |Hannah Han |Matthias Schneider |Georg Meisl |Hannah Nguyen | +2 more

AbstractSegments of proteins with high β-strand propensity can self-associate to form amyloid fibrils implicated in many diseases. We describe a general approach to bind such segments in β-strand and β-hairpin conformations using de novo designed scaffolds that contain deep peptide-binding clefts. The designs bind their cognate peptides in vitro with nanomolar affinities.