Revealin. The structural details of huntingtin fibrils using small-angle neutron scattering

Christopher Stanley; Helen P. McWilliams-Koeppen; Tatiana Perevozchikova; Erica L. Rowe; Valerie Berthelier

doi:10.1109/BSEC.2014.6867753

Revealin. The structural details of huntingtin fibrils using small-angle neutron scattering

Christopher Stanley, Helen P. McWilliams-Koeppen, Tatiana Perevozchikova, Erica L. Rowe, Valerie Berthelier

Scalable Biomedical Modeling

Research output: Chapter in Book/Report/Conference proceeding › Conference contribution › peer-review

Abstract

Huntington's disease (HD) involves an abnormally expanded polyglutamine sequence in huntingtin (Htt) protein that makes it highly susceptible to aggregate. A current challenge is to map ou. The aggregation pathway by identifyin. The various precursor structures and establishin. Their roles i. The disease. While it is highly suspected tha. The early oligomer species are responsible for toxicity, characterizin. The end-state fibril structure is also a necessary step toward discoverin. The underlying mechanisms of early aggregate formation. We are actively investigating Htt structural kinetics an. The resulting fibrils using small-angle neutron scattering (SANS). Here, we report o. The characterization of fibrils from Htt-exon1-Q₄₀ - a disease relevant Htt peptide as it contains a pathologically expanded glutamine repeat sequence and a proline-rich region. SANS o. The end-state fibrils revealed structural similarities t. The Perutz ß-helixhollow cylinder model as opposed t. The more commonly observed steric zipper structure found for many other amyloid fibrils. The structural details we have identified contribute toward elucidatin. The mechanism of pathological Htt assembly.

Original language	English
Title of host publication	Proceedings of the 2014 Biomedical Sciences and Engineering Conference - 5th Annual ORNL Biomedical Sciences and Engineering Conference
Subtitle of host publication	Collaborative Biomedical Innovations - The Multi-Scale Brain: Spanning Molecular, Cellular, Systems, Cognitive, Behavioral, and Clinical Neuroscience, BSEC 2014
Publisher	Institute of Electrical and Electronics Engineers Inc.
ISBN (Electronic)	9781479941599
DOIs	https://doi.org/10.1109/BSEC.2014.6867753
State	Published - Jul 29 2014
Event	5th Annual ORNL Biomedical Sciences and Engineering Conference: Collaborative Biomedical Innovations, BSEC 2014 - Oak Ridge, United States Duration: May 6 2014 → May 8 2014

Publication series

Name	Proceedings of the 2014 Biomedical Sciences and Engineering Conference - 5th Annual ORNL Biomedical Sciences and Engineering Conference: Collaborative Biomedical Innovations - The Multi-Scale Brain: Spanning Molecular, Cellular, Systems, Cognitive, Behavioral, and Clinical Neuroscience, BSEC 2014

Conference

Conference	5th Annual ORNL Biomedical Sciences and Engineering Conference: Collaborative Biomedical Innovations, BSEC 2014
Country/Territory	United States
City	Oak Ridge
Period	05/6/14 → 05/8/14

Bibliographical note

Publisher Copyright:
© 2014 IEEE.

Keywords

Huntington's disease
amyloid
polyglutamine
protein aggregation
solution scattering

Access to Document

10.1109/BSEC.2014.6867753

Cite this

Stanley, C., McWilliams-Koeppen, H. P., Perevozchikova, T., Rowe, E. L., & Berthelier, V. (2014). Revealin. The structural details of huntingtin fibrils using small-angle neutron scattering. In Proceedings of the 2014 Biomedical Sciences and Engineering Conference - 5th Annual ORNL Biomedical Sciences and Engineering Conference: Collaborative Biomedical Innovations - The Multi-Scale Brain: Spanning Molecular, Cellular, Systems, Cognitive, Behavioral, and Clinical Neuroscience, BSEC 2014 Article 6867753 (Proceedings of the 2014 Biomedical Sciences and Engineering Conference - 5th Annual ORNL Biomedical Sciences and Engineering Conference: Collaborative Biomedical Innovations - The Multi-Scale Brain: Spanning Molecular, Cellular, Systems, Cognitive, Behavioral, and Clinical Neuroscience, BSEC 2014). Institute of Electrical and Electronics Engineers Inc.. https://doi.org/10.1109/BSEC.2014.6867753

Stanley, Christopher ; McWilliams-Koeppen, Helen P. ; Perevozchikova, Tatiana et al. / Revealin. The structural details of huntingtin fibrils using small-angle neutron scattering. Proceedings of the 2014 Biomedical Sciences and Engineering Conference - 5th Annual ORNL Biomedical Sciences and Engineering Conference: Collaborative Biomedical Innovations - The Multi-Scale Brain: Spanning Molecular, Cellular, Systems, Cognitive, Behavioral, and Clinical Neuroscience, BSEC 2014. Institute of Electrical and Electronics Engineers Inc., 2014. (Proceedings of the 2014 Biomedical Sciences and Engineering Conference - 5th Annual ORNL Biomedical Sciences and Engineering Conference: Collaborative Biomedical Innovations - The Multi-Scale Brain: Spanning Molecular, Cellular, Systems, Cognitive, Behavioral, and Clinical Neuroscience, BSEC 2014).

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title = "Revealin. The structural details of huntingtin fibrils using small-angle neutron scattering",

abstract = "Huntington's disease (HD) involves an abnormally expanded polyglutamine sequence in huntingtin (Htt) protein that makes it highly susceptible to aggregate. A current challenge is to map ou. The aggregation pathway by identifyin. The various precursor structures and establishin. Their roles i. The disease. While it is highly suspected tha. The early oligomer species are responsible for toxicity, characterizin. The end-state fibril structure is also a necessary step toward discoverin. The underlying mechanisms of early aggregate formation. We are actively investigating Htt structural kinetics an. The resulting fibrils using small-angle neutron scattering (SANS). Here, we report o. The characterization of fibrils from Htt-exon1-Q40 - a disease relevant Htt peptide as it contains a pathologically expanded glutamine repeat sequence and a proline-rich region. SANS o. The end-state fibrils revealed structural similarities t. The Perutz {\ss}-helixhollow cylinder model as opposed t. The more commonly observed steric zipper structure found for many other amyloid fibrils. The structural details we have identified contribute toward elucidatin. The mechanism of pathological Htt assembly.",

keywords = "Huntington's disease, amyloid, polyglutamine, protein aggregation, solution scattering",

author = "Christopher Stanley and McWilliams-Koeppen, {Helen P.} and Tatiana Perevozchikova and Rowe, {Erica L.} and Valerie Berthelier",

note = "Publisher Copyright: {\textcopyright} 2014 IEEE.; 5th Annual ORNL Biomedical Sciences and Engineering Conference: Collaborative Biomedical Innovations, BSEC 2014 ; Conference date: 06-05-2014 Through 08-05-2014",

year = "2014",

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doi = "10.1109/BSEC.2014.6867753",

language = "English",

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publisher = "Institute of Electrical and Electronics Engineers Inc.",

booktitle = "Proceedings of the 2014 Biomedical Sciences and Engineering Conference - 5th Annual ORNL Biomedical Sciences and Engineering Conference",

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Stanley, C, McWilliams-Koeppen, HP, Perevozchikova, T, Rowe, EL & Berthelier, V 2014, Revealin. The structural details of huntingtin fibrils using small-angle neutron scattering. in Proceedings of the 2014 Biomedical Sciences and Engineering Conference - 5th Annual ORNL Biomedical Sciences and Engineering Conference: Collaborative Biomedical Innovations - The Multi-Scale Brain: Spanning Molecular, Cellular, Systems, Cognitive, Behavioral, and Clinical Neuroscience, BSEC 2014., 6867753, Proceedings of the 2014 Biomedical Sciences and Engineering Conference - 5th Annual ORNL Biomedical Sciences and Engineering Conference: Collaborative Biomedical Innovations - The Multi-Scale Brain: Spanning Molecular, Cellular, Systems, Cognitive, Behavioral, and Clinical Neuroscience, BSEC 2014, Institute of Electrical and Electronics Engineers Inc., 5th Annual ORNL Biomedical Sciences and Engineering Conference: Collaborative Biomedical Innovations, BSEC 2014, Oak Ridge, United States, 05/6/14. https://doi.org/10.1109/BSEC.2014.6867753

Revealin. The structural details of huntingtin fibrils using small-angle neutron scattering. / Stanley, Christopher; McWilliams-Koeppen, Helen P.; Perevozchikova, Tatiana et al.
Proceedings of the 2014 Biomedical Sciences and Engineering Conference - 5th Annual ORNL Biomedical Sciences and Engineering Conference: Collaborative Biomedical Innovations - The Multi-Scale Brain: Spanning Molecular, Cellular, Systems, Cognitive, Behavioral, and Clinical Neuroscience, BSEC 2014. Institute of Electrical and Electronics Engineers Inc., 2014. 6867753 (Proceedings of the 2014 Biomedical Sciences and Engineering Conference - 5th Annual ORNL Biomedical Sciences and Engineering Conference: Collaborative Biomedical Innovations - The Multi-Scale Brain: Spanning Molecular, Cellular, Systems, Cognitive, Behavioral, and Clinical Neuroscience, BSEC 2014).

Research output: Chapter in Book/Report/Conference proceeding › Conference contribution › peer-review

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AU - McWilliams-Koeppen, Helen P.

AU - Perevozchikova, Tatiana

AU - Rowe, Erica L.

AU - Berthelier, Valerie

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N2 - Huntington's disease (HD) involves an abnormally expanded polyglutamine sequence in huntingtin (Htt) protein that makes it highly susceptible to aggregate. A current challenge is to map ou. The aggregation pathway by identifyin. The various precursor structures and establishin. Their roles i. The disease. While it is highly suspected tha. The early oligomer species are responsible for toxicity, characterizin. The end-state fibril structure is also a necessary step toward discoverin. The underlying mechanisms of early aggregate formation. We are actively investigating Htt structural kinetics an. The resulting fibrils using small-angle neutron scattering (SANS). Here, we report o. The characterization of fibrils from Htt-exon1-Q40 - a disease relevant Htt peptide as it contains a pathologically expanded glutamine repeat sequence and a proline-rich region. SANS o. The end-state fibrils revealed structural similarities t. The Perutz ß-helixhollow cylinder model as opposed t. The more commonly observed steric zipper structure found for many other amyloid fibrils. The structural details we have identified contribute toward elucidatin. The mechanism of pathological Htt assembly.

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KW - Huntington's disease

KW - amyloid

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T3 - Proceedings of the 2014 Biomedical Sciences and Engineering Conference - 5th Annual ORNL Biomedical Sciences and Engineering Conference: Collaborative Biomedical Innovations - The Multi-Scale Brain: Spanning Molecular, Cellular, Systems, Cognitive, Behavioral, and Clinical Neuroscience, BSEC 2014

BT - Proceedings of the 2014 Biomedical Sciences and Engineering Conference - 5th Annual ORNL Biomedical Sciences and Engineering Conference

PB - Institute of Electrical and Electronics Engineers Inc.

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Stanley C, McWilliams-Koeppen HP, Perevozchikova T, Rowe EL, Berthelier V. Revealin. The structural details of huntingtin fibrils using small-angle neutron scattering. In Proceedings of the 2014 Biomedical Sciences and Engineering Conference - 5th Annual ORNL Biomedical Sciences and Engineering Conference: Collaborative Biomedical Innovations - The Multi-Scale Brain: Spanning Molecular, Cellular, Systems, Cognitive, Behavioral, and Clinical Neuroscience, BSEC 2014. Institute of Electrical and Electronics Engineers Inc. 2014. 6867753. (Proceedings of the 2014 Biomedical Sciences and Engineering Conference - 5th Annual ORNL Biomedical Sciences and Engineering Conference: Collaborative Biomedical Innovations - The Multi-Scale Brain: Spanning Molecular, Cellular, Systems, Cognitive, Behavioral, and Clinical Neuroscience, BSEC 2014). doi: 10.1109/BSEC.2014.6867753

Revealin. The structural details of huntingtin fibrils using small-angle neutron scattering

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Keywords

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