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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Dearborn</name><affiliation wicri:level="2"><nlm:affiliation>From the Laboratory of Structural Biology Research, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>From the Laboratory of Structural Biology Research, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Wall, Joseph S" sort="Wall, Joseph S" uniqKey="Wall J" first="Joseph S" last="Wall">Joseph S. Wall</name><affiliation wicri:level="2"><nlm:affiliation>the Department of Biology, Brookhaven National Laboratory, Upton, New York 19973.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>the Department of Biology, Brookhaven National Laboratory, Upton</wicri:cityArea></affiliation></author><author><name sortKey="Cheng, Naiqian" sort="Cheng, Naiqian" uniqKey="Cheng N" first="Naiqian" last="Cheng">Naiqian Cheng</name><affiliation wicri:level="2"><nlm:affiliation>From the Laboratory of Structural Biology Research, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>From the Laboratory of Structural Biology Research, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Heymann, J Bernard" sort="Heymann, J Bernard" uniqKey="Heymann J" first="J Bernard" last="Heymann">J Bernard Heymann</name><affiliation wicri:level="2"><nlm:affiliation>From the Laboratory of Structural Biology Research, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>From the Laboratory of Structural Biology Research, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Kajava, Andrey V" sort="Kajava, Andrey V" uniqKey="Kajava A" first="Andrey V" last="Kajava">Andrey V. Kajava</name><affiliation wicri:level="1"><nlm:affiliation>the Centre de Recherches de Biochimie Macromoléculaire, CNRS, University of Montpellier, Montpellier 34172, France, the University ITMO, Institute of Bioengineering, 197101 St. Petersburg, Russia.</nlm:affiliation><country xml:lang="fr">Russie</country><wicri:regionArea>the Centre de Recherches de Biochimie Macromoléculaire, CNRS, University of Montpellier, Montpellier 34172, France, the University ITMO, Institute of Bioengineering, 197101 St. Petersburg</wicri:regionArea><wicri:noRegion>197101 St. Petersburg</wicri:noRegion></affiliation></author><author><name sortKey="Varkey, Jobin" sort="Varkey, Jobin" uniqKey="Varkey J" first="Jobin" last="Varkey">Jobin Varkey</name><affiliation wicri:level="4"><nlm:affiliation>the Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California 90033, and Karunya University, Coimbatore, Tamil Nadu 641 114, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>the Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California 90033, and Karunya University, Coimbatore, Tamil Nadu 641 114</wicri:regionArea><orgName type="university">Université de Californie du Sud</orgName><placeName><settlement type="city">Los Angeles</settlement><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Langen, Ralf" sort="Langen, Ralf" uniqKey="Langen R" first="Ralf" last="Langen">Ralf Langen</name><affiliation wicri:level="4"><nlm:affiliation>the Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California 90033, and.</nlm:affiliation><orgName type="university">Université de Californie du Sud</orgName><country>États-Unis</country><placeName><settlement type="city">Los Angeles</settlement><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Steven, Alasdair C" sort="Steven, Alasdair C" uniqKey="Steven A" first="Alasdair C" last="Steven">Alasdair C. Steven</name><affiliation wicri:level="1"><nlm:affiliation>From the Laboratory of Structural Biology Research, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, stevena@mail.nih.gov.</nlm:affiliation><country wicri:rule="url">Israël</country><wicri:regionArea>From the Laboratory of Structural Biology Research, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892</wicri:regionArea><wicri:noRegion>Maryland 20892</wicri:noRegion></affiliation></author></analytic><series><title level="j">The Journal of biological chemistry</title><idno type="eISSN">1083-351X</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term><term>Amyloid (chemistry)</term><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><term>Molecular Sequence Data</term><term>Protein Structure, Secondary</term><term>Sequence Homology, Amino Acid</term><term>alpha-Synuclein (chemistry)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Amyloid</term><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Lewy Bodies</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Binding Sites</term><term>Cryoelectron Microscopy</term><term>Humans</term><term>Image Processing, Computer-Assisted</term><term>Ions</term><term>Microscopy, Electron, Scanning Transmission</term><term>Molecular Sequence Data</term><term>Protein Structure, Secondary</term><term>Sequence Homology, Amino Acid</term></keywords></textClass></profileDesc></teiHeader><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></TEI><affiliations><list><country><li>Inde</li><li>Israël</li><li>Russie</li><li>États-Unis</li></country><region><li>Californie</li><li>Maryland</li><li>État de New York</li></region><settlement><li>Los Angeles</li></settlement><orgName><li>Université de Californie du Sud</li></orgName></list><tree><country name="États-Unis"><region name="Maryland"><name sortKey="Dearborn, Altaira D" sort="Dearborn, Altaira D" uniqKey="Dearborn A" first="Altaira D" last="Dearborn">Altaira D. Dearborn</name></region><name sortKey="Cheng, Naiqian" sort="Cheng, Naiqian" uniqKey="Cheng N" first="Naiqian" last="Cheng">Naiqian Cheng</name><name sortKey="Heymann, J Bernard" sort="Heymann, J Bernard" uniqKey="Heymann J" first="J Bernard" last="Heymann">J Bernard Heymann</name><name sortKey="Langen, Ralf" sort="Langen, Ralf" uniqKey="Langen R" first="Ralf" last="Langen">Ralf Langen</name><name sortKey="Wall, Joseph S" sort="Wall, Joseph S" uniqKey="Wall J" first="Joseph S" last="Wall">Joseph S. Wall</name></country><country name="Russie"><noRegion><name sortKey="Kajava, Andrey V" sort="Kajava, Andrey V" uniqKey="Kajava A" first="Andrey V" last="Kajava">Andrey V. Kajava</name></noRegion></country><country name="Inde"><region name="Californie"><name sortKey="Varkey, Jobin" sort="Varkey, Jobin" uniqKey="Varkey J" first="Jobin" last="Varkey">Jobin Varkey</name></region></country><country name="Israël"><noRegion><name sortKey="Steven, Alasdair C" sort="Steven, Alasdair C" uniqKey="Steven A" first="Alasdair C" last="Steven">Alasdair C. Steven</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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