α-Synuclein Amyloid Fibrils with Two Entwined, Asymmetrically Associated Protofibrils.
Identifieur interne : 001891 ( Ncbi/Checkpoint ); précédent : 001890; suivant : 001892α-Synuclein Amyloid Fibrils with Two Entwined, Asymmetrically Associated Protofibrils.
Auteurs : Altaira D. Dearborn [États-Unis] ; Joseph S. Wall [États-Unis] ; Naiqian Cheng [États-Unis] ; J Bernard Heymann [États-Unis] ; Andrey V. Kajava [Russie] ; Jobin Varkey [Inde] ; Ralf Langen [États-Unis] ; Alasdair C. Steven [Israël]Source :
- The Journal of biological chemistry [ 1083-351X ] ; 2016.
English descriptors
- KwdEn :
- Amino Acid Sequence, Amyloid (chemistry), Binding Sites, Cryoelectron Microscopy, Humans, Image Processing, Computer-Assisted, Ions, Lewy Bodies (metabolism), Microscopy, Electron, Scanning Transmission, Molecular Sequence Data, Protein Structure, Secondary, Sequence Homology, Amino Acid, alpha-Synuclein (chemistry).
- MESH :
- chemical , chemistry : Amyloid, alpha-Synuclein.
- metabolism : Lewy Bodies.
- Amino Acid Sequence, Binding Sites, Cryoelectron Microscopy, Humans, Image Processing, Computer-Assisted, Ions, Microscopy, Electron, Scanning Transmission, Molecular Sequence Data, Protein Structure, Secondary, Sequence Homology, Amino Acid.
Abstract
Parkinson disease and other progressive neurodegenerative conditions are characterized by the intracerebral presence of Lewy bodies, containing amyloid fibrils of α-synuclein. We used cryo-electron microscopy and scanning transmission electron microscopy (STEM) to study in vitro-assembled fibrils. These fibrils are highly polymorphic. Focusing on twisting fibrils with an inter-crossover spacing of 77 nm, our reconstructions showed them to consist of paired protofibrils. STEM mass per length data gave one subunit per 0.47 nm axial rise per protofibril, consistent with a superpleated β-structure. The STEM images show two thread-like densities running along each of these fibrils, which we interpret as ladders of metal ions. These threads confirmed the two-protofibril architecture of the 77-nm twisting fibrils and allowed us to identify this morphotype in STEM micrographs. Some other, but not all, fibril morphotypes also exhibit dense threads, implying that they also present a putative metal binding site. We propose a molecular model for the protofibril and suggest that polymorphic variant fibrils have different numbers of protofibrils that are associated differently.
DOI: 10.1074/jbc.M115.698787
PubMed: 26644467
Affiliations:
- Inde, Israël, Russie, États-Unis
- Californie, Maryland, État de New York
- Los Angeles
- Université de Californie du Sud
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<term>Binding Sites</term>
<term>Cryoelectron Microscopy</term>
<term>Humans</term>
<term>Image Processing, Computer-Assisted</term>
<term>Ions</term>
<term>Lewy Bodies (metabolism)</term>
<term>Microscopy, Electron, Scanning Transmission</term>
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<term>Protein Structure, Secondary</term>
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<term>Cryoelectron Microscopy</term>
<term>Humans</term>
<term>Image Processing, Computer-Assisted</term>
<term>Ions</term>
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<front><div type="abstract" xml:lang="en">Parkinson disease and other progressive neurodegenerative conditions are characterized by the intracerebral presence of Lewy bodies, containing amyloid fibrils of α-synuclein. We used cryo-electron microscopy and scanning transmission electron microscopy (STEM) to study in vitro-assembled fibrils. These fibrils are highly polymorphic. Focusing on twisting fibrils with an inter-crossover spacing of 77 nm, our reconstructions showed them to consist of paired protofibrils. STEM mass per length data gave one subunit per 0.47 nm axial rise per protofibril, consistent with a superpleated β-structure. The STEM images show two thread-like densities running along each of these fibrils, which we interpret as ladders of metal ions. These threads confirmed the two-protofibril architecture of the 77-nm twisting fibrils and allowed us to identify this morphotype in STEM micrographs. Some other, but not all, fibril morphotypes also exhibit dense threads, implying that they also present a putative metal binding site. We propose a molecular model for the protofibril and suggest that polymorphic variant fibrils have different numbers of protofibrils that are associated differently.</div>
</front>
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