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Merle, D.A.* ; Witternigg, A.* ; Tam-Amersdorfer, C.* ; Hartlmüller, C. ; Spreitzer, E.* ; Schrank, E.* ; Wagner-Lichtenegger, S.* ; Werzer, O.* ; Zangger, K.* ; Kungl, A.J.* ; Madl, T.* ; Meyer, N.H.* ; Falsone, S.F.*

Increased aggregation tendency of alpha-synuclein in a fully disordered protein complex.

J. Mol. Biol. 431, 2581-2598 (2019)
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
The recent discovery of biologically active fully disordered, so called random fuzzy protein protein interactions leads to the question of how the high flexibility of these protein complexes correlates to aggregation and pathologic misfolding.We identify the structural mechanism by which a random fuzzy protein complex composed of the intrinsically disordered proteins alpha-Synuclein and SERF1a is able to potentiate cytotoxic aggregation. A structural model derived from an integrated NMR/SAXS analysis of the reconstituted aSyn:SERF1a complex enabled us to observe the partial deprotection of one precise aSyn amyloid nucleation element in the fully unstructured ensemble. This minimal exposure was sufficient to increase the amyloidogenic tendency of SERF1a-bound aSyn.Our findings provide a structural explanation of the previously observed pro-amyloid activity of SERF1a. They further demonstrate that random fuzziness can trigger a structurally organized disease-associated reaction such as amyloid polymerization.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Fuzzy Complexes ; Intrinsically Disordered Proteins ; Amyloids ; Alpha Synuclein ; Moag-4/serf; Nmr; Promotes; Mechanism; Dynamics; Binding; Order
ISSN (print) / ISBN 0022-2836
e-ISSN 1089-8638
Quellenangaben Band: 431, Heft: 14, Seiten: 2581-2598 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort 24-28 Oval Rd, London Nw1 7dx, England
Begutachtungsstatus Peer reviewed