TY - GEN
T1 - Revealin. The structural details of huntingtin fibrils using small-angle neutron scattering
AU - Stanley, Christopher
AU - McWilliams-Koeppen, Helen P.
AU - Perevozchikova, Tatiana
AU - Rowe, Erica L.
AU - Berthelier, Valerie
N1 - Publisher Copyright:
© 2014 IEEE.
PY - 2014/7/29
Y1 - 2014/7/29
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.
AB - 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.
KW - Huntington's disease
KW - amyloid
KW - polyglutamine
KW - protein aggregation
KW - solution scattering
UR - http://www.scopus.com/inward/record.url?scp=84934777068&partnerID=8YFLogxK
U2 - 10.1109/BSEC.2014.6867753
DO - 10.1109/BSEC.2014.6867753
M3 - Conference contribution
AN - SCOPUS:84934777068
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.
T2 - 5th Annual ORNL Biomedical Sciences and Engineering Conference: Collaborative Biomedical Innovations, BSEC 2014
Y2 - 6 May 2014 through 8 May 2014
ER -