Sökning: WFRF:(Horváth István)
> (2010-2014) >
Mechanisms of Prote...
Mechanisms of Protein Oligomerization : Inhibitor of Functional Amyloids Templates α-Synuclein Fibrillation
-
- Horvath, Istvan (författare)
- Umeå universitet,Kemiska institutionen
-
- Weise, Christoph F (författare)
- Umeå universitet,Kemiska institutionen
-
- Andersson, Emma K (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik,Umeå Centre for Microbial Research (UCMR)
-
visa fler...
-
- Chorell, Erik (författare)
- Umeå universitet,Kemiska institutionen
-
- Sellstedt, Magnus (författare)
- Umeå universitet,Kemiska institutionen
-
- Bengtsson, Christoffer (författare)
- Umeå universitet,Kemiska institutionen
-
- Olofsson, Anders (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
-
- Hultgren, Scott J (författare)
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110, United States
-
- Chapman, Matthew (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik,Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109-1048, United States
-
- Wolf-Watz, Magnus (författare)
- Umeå universitet,Kemiska institutionen
-
- Almqvist, Fredrik (författare)
- Umeå universitet,Kemiska institutionen,Umeå Centre for Microbial Research (UCMR)
-
- Wittung-Stafshede, Pernilla (författare)
- Umeå universitet,Kemiska institutionen
-
visa färre...
-
(creator_code:org_t)
- 2012-02-09
- 2012
- Engelska.
-
Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 134:7, s. 3439-3444
- Relaterad länk:
-
https://doi.org/10.1...
-
visa fler...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- Small organic molecules that inhibit functional bacterial amyloid fibers, curli, are promising new antibiotics. Here we investigated the mechanism by which the ring-fused 2-pyridone FN075 inhibits fibrillation of the curli protein CsgA. Using a variety of biophysical techniques, we found that FN075 promotes CsgA to form off-pathway, non-amyloidogenic oligomeric species. In light of the generic properties of amyloids, we tested whether FN075 would also affect the fibrillation reaction of human α-synuclein, an amyloid-forming protein involved in Parkinson's disease. Surprisingly, FN075 stimulates α-synuclein amyloid fiber formation as measured by thioflavin T emission, electron microscopy (EM), and atomic force microscopy (AFM). NMR data on (15)N-labeled α-synuclein show that upon FN075 addition, α-synuclein oligomers with 7 nm radius form in which the C-terminal 40 residues remain disordered and solvent exposed. The polypeptides in these oligomers contain β-like secondary structure, and the oligomers are detectable by AFM, EM, and size-exclusion chromatography (SEC). Taken together, FN075 triggers oligomer formation of both proteins: in the case of CsgA, the oligomers do not proceed to fibers, whereas for α-synuclein, the oligomers are poised to rapidly form fibers. We conclude that there is a fine balance between small-molecule inhibition and templation that depends on protein chemistry.
Ämnesord
- NATURVETENSKAP -- Kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Horvath, Istvan
-
Weise, Christoph ...
-
Andersson, Emma ...
-
Chorell, Erik
-
Sellstedt, Magnu ...
-
Bengtsson, Chris ...
-
visa fler...
-
Olofsson, Anders
-
Hultgren, Scott ...
-
Chapman, Matthew
-
Wolf-Watz, Magnu ...
-
Almqvist, Fredri ...
-
Wittung-Stafshed ...
-
visa färre...
- Om ämnet
-
- NATURVETENSKAP
-
NATURVETENSKAP
-
och Kemi
- Artiklar i publikationen
-
Journal of the A ...
- Av lärosätet
-
Umeå universitet