Cryo-electron tomography provides topological insights into mutant huntingtin exon 1 and polyQ aggregates

Galaz-Montoya, Jesús G.; Shahmoradian, Sarah H.; Shen, Koning; Frydman, Judith; Chiu, Wah

doi:10.1038/s42003-021-02360-2

Cryo-electron tomography provides topological insights into mutant huntingtin exon 1 and polyQ aggregates

Journal Article · Thu Jul 08 00:00:00 EDT 2021 · Communications Biology

DOI:https://doi.org/10.1038/s42003-021-02360-2· OSTI ID:1814841

^[1]; Shahmoradian, Sarah H. ^[2]; Shen, Koning ^[3]; ^[3]; ^[4]

Stanford Univ., CA (United States). James H. Clark Center
Paul Scherrer Inst. (PSI), Villigen (Switzerland). Lab. of Biomolecular Research
Stanford Univ., CA (United States)
Stanford Univ., CA (United States). James H. Clark Center; SLAC National Accelerator Lab., Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)

Huntington disease (HD) is a neurodegenerative trinucleotide repeat disorder caused by an expanded poly-glutamine (polyQ) tract in the mutant huntingtin (mHTT) protein. The formation and topology of filamentous mHTT inclusions in the brain (hallmarks of HD implicated in neurotoxicity) remain elusive. Using cryo-electron tomography and subtomogram averaging, here we show that mHTT exon 1 and polyQ-only aggregates in vitro are structurally heterogenous and filamentous, similar to prior observations with other methods. Yet, we find filaments in both types of aggregates under ~2 nm in width, thinner than previously reported, and regions forming large sheets. In addition, our data show a prevalent subpopulation of filaments exhibiting a lumpy slab morphology in both aggregates, supportive of the polyQ core model. This provides a basis for future cryoET studies of various aggregated mHTT and polyQ constructs to improve their structure-based modeling as well as their identification in cells without fusion tags.

View Accepted Manuscript (DOE)

Research Organization:: SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC02-76SF00515

OSTI ID:: 1814841

Journal Information:: Communications Biology, Journal Name: Communications Biology Journal Issue: 1 Vol. 4; ISSN 2399-3642

Publisher:: Springer NatureCopyright Statement

Country of Publication:: United States

Language:: English

References (81)

Use of Fluorescent Probes: Their Effect on Cell Biology and Limitations Jensen, Ellen C. The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology, Vol. 295, Issue 12 https://doi.org/10.1002/ar.22602	journal	October 2012
Sub-Diffraction Imaging of Huntingtin Protein Aggregates by Fluorescence Blink-Microscopy and Atomic Force Microscopy Duim, Whitney C.; Chen, Bryan; Frydman, Judith ChemPhysChem, Vol. 12, Issue 13 https://doi.org/10.1002/cphc.201100392	journal	July 2011
UCSF Chimera?A visualization system for exploratory research and analysis Pettersen, Eric F.; Goddard, Thomas D.; Huang, Conrad C. Journal of Computational Chemistry, Vol. 25, Issue 13 https://doi.org/10.1002/jcc.20084	journal	January 2004
Three-Dimensional reconstruction of single particles from random and nonrandom tilt series Radermacher, Michael Journal of Electron Microscopy Technique, Vol. 9, Issue 4 https://doi.org/10.1002/jemt.1060090405	journal	August 1988
Polyglutamine inclusion body toxicity Albin, Roger L. Movement Disorders, Vol. 32, Issue 12 https://doi.org/10.1002/mds.27226	journal	November 2017
Polyglutamine aggregation behavior in vitro supports a recruitment mechanism of cytotoxicity Chen, Songming; Berthelier, Valerie; Yang, Wen Journal of Molecular Biology, Vol. 311, Issue 1 https://doi.org/10.1006/jmbi.2001.4850	journal	August 2001
Computer Visualization of Three-Dimensional Image Data Using IMOD Kremer, James R.; Mastronarde, David N.; McIntosh, J. Richard Journal of Structural Biology, Vol. 116, Issue 1 https://doi.org/10.1006/jsbi.1996.0013	journal	January 1996
The advent of structural biology in situ by single particle cryo-electron tomography Galaz-Montoya, Jesús G.; Ludtke, Steven J. Biophysics Reports, Vol. 3, Issue 1-3 https://doi.org/10.1007/s41048-017-0040-0	journal	May 2017
Accelerating electron tomography reconstruction algorithm ICON with GPU Chen, Yu; Wang, Zihao; Zhang, Jingrong Biophysics Reports, Vol. 3, Issue 1-3 https://doi.org/10.1007/s41048-017-0041-z	journal	June 2017
A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes Macdonald, M. Cell, Vol. 72, Issue 6 https://doi.org/10.1016/0092-8674(93)90585-E	journal	March 1993
Formation of Neuronal Intranuclear Inclusions Underlies the Neurological Dysfunction in Mice Transgenic for the HD Mutation Davies, Stephen W.; Turmaine, Mark; Cozens, Barbara A. Cell, Vol. 90, Issue 3 https://doi.org/10.1016/S0092-8674(00)80513-9	journal	August 1997
Huntingtin-Encoded Polyglutamine Expansions Form Amyloid-like Protein Aggregates In Vitro and In Vivo Scherzinger, Eberhard; Lurz, Rudi; Turmaine, Mark Cell, Vol. 90, Issue 3 https://doi.org/10.1016/S0092-8674(00)80514-0	journal	August 1997
Exon 1 of the HD Gene with an Expanded CAG Repeat Is Sufficient to Cause a Progressive Neurological Phenotype in Transgenic Mice Mangiarini, Laura; Sathasivam, Kirupa; Seller, Mary Cell, Vol. 87, Issue 3 https://doi.org/10.1016/S0092-8674(00)81369-0	journal	November 1996
Therapies targeting DNA and RNA in Huntington's disease Wild, Edward J.; Tabrizi, Sarah J. The Lancet Neurology, Vol. 16, Issue 10 https://doi.org/10.1016/S1474-4422(17)30280-6	journal	October 2017
In Situ Architecture and Cellular Interactions of PolyQ Inclusions Bäuerlein, Felix J. B.; Saha, Itika; Mishra, Archana Cell, Vol. 171, Issue 1 https://doi.org/10.1016/j.cell.2017.08.009	journal	September 2017
Neutralizing Antibodies Inhibit Chikungunya Virus Budding at the Plasma Membrane Jin, Jing; Galaz-Montoya, Jesús G.; Sherman, Michael B. Cell Host & Microbe, Vol. 24, Issue 3 https://doi.org/10.1016/j.chom.2018.07.018	journal	September 2018
Structural Characterization of Polyglutamine Fibrils by Solid-State NMR Spectroscopy Schneider, Robert; Schumacher, Miria C.; Mueller, Henrik Journal of Molecular Biology, Vol. 412, Issue 1 https://doi.org/10.1016/j.jmb.2011.06.045	journal	September 2011
Physical Chemistry of Polyglutamine: Intriguing Tales of a Monotonous Sequence Wetzel, Ronald Journal of Molecular Biology, Vol. 421, Issue 4-5 https://doi.org/10.1016/j.jmb.2012.01.030	journal	August 2012
Self-assembly of Mutant Huntingtin Exon-1 Fragments into Large Complex Fibrillar Structures Involves Nucleated Branching Wagner, Anne S.; Politi, Antonio Z.; Ast, Anne Journal of Molecular Biology, Vol. 430, Issue 12 https://doi.org/10.1016/j.jmb.2018.03.017	journal	June 2018
Protofilament Structure and Supramolecular Polymorphism of Aggregated Mutant Huntingtin Exon 1 Boatz, Jennifer C.; Piretra, Talia; Lasorsa, Alessia Journal of Molecular Biology, Vol. 432, Issue 16 https://doi.org/10.1016/j.jmb.2020.06.021	journal	July 2020
Huntington disease: A quarter century of progress since the gene discovery Testa, Claudia M.; Jankovic, Joseph Journal of the Neurological Sciences, Vol. 396 https://doi.org/10.1016/j.jns.2018.09.022	journal	January 2019
Electron tomography reveals diverse conformations of integrin αIIbβ3 in the active state Iwasaki, Kenji; Mitsuoka, Kaoru; Fujiyoshi, Yoshinori Journal of Structural Biology, Vol. 150, Issue 3 https://doi.org/10.1016/j.jsb.2005.03.005	journal	June 2005
Automated electron microscope tomography using robust prediction of specimen movements Mastronarde, David N. Journal of Structural Biology, Vol. 152, Issue 1 https://doi.org/10.1016/j.jsb.2005.07.007	journal	October 2005
Classification and 3D averaging with missing wedge correction in biological electron tomography☆ Bartesaghi, A.; Sprechmann, P.; Liu, J. Journal of Structural Biology, Vol. 162, Issue 3 https://doi.org/10.1016/j.jsb.2008.02.008	journal	June 2008
Automated segmentation of electron tomograms for a quantitative description of actin filament networks Rigort, Alexander; Günther, David; Hegerl, Reiner Journal of Structural Biology, Vol. 177, Issue 1 https://doi.org/10.1016/j.jsb.2011.08.012	journal	January 2012
Automated tracing of filaments in 3D electron tomography reconstructions using Sculptor and Situs Rusu, Mirabela; Starosolski, Zbigniew; Wahle, Manuel Journal of Structural Biology, Vol. 178, Issue 2 https://doi.org/10.1016/j.jsb.2012.03.001	journal	May 2012
M-free: Scoring the reference bias in sub-tomogram averaging and template matching Yu, Zhou; Frangakis, Achilleas S. Journal of Structural Biology, Vol. 187, Issue 1 https://doi.org/10.1016/j.jsb.2014.05.007	journal	July 2014
Single particle tomography in EMAN2 Galaz-Montoya, Jesús G.; Flanagan, John; Schmid, Michael F. Journal of Structural Biology, Vol. 190, Issue 3 https://doi.org/10.1016/j.jsb.2015.04.016	journal	June 2015
Alignment algorithms and per-particle CTF correction for single particle cryo-electron tomography Galaz-Montoya, Jesús G.; Hecksel, Corey W.; Baldwin, Philip R. Journal of Structural Biology, Vol. 194, Issue 3 https://doi.org/10.1016/j.jsb.2016.03.018	journal	June 2016
ICON: 3D reconstruction with ‘missing-information’ restoration in biological electron tomography Deng, Yuchen; Chen, Yu; Zhang, Yan Journal of Structural Biology, Vol. 195, Issue 1 https://doi.org/10.1016/j.jsb.2016.04.004	journal	July 2016
Huntingtin Lowering Strategies for Disease Modification in Huntington’s Disease Tabrizi, Sarah J.; Ghosh, Rhia; Leavitt, Blair R. Neuron, Vol. 101, Issue 5 https://doi.org/10.1016/j.neuron.2019.01.039	journal	March 2019
Exploring the structure and function paradigm Redfern, Oliver C.; Dessailly, Benoit; Orengo, Christine A. Current Opinion in Structural Biology, Vol. 18, Issue 3 https://doi.org/10.1016/j.sbi.2008.05.007	journal	June 2008
Cryo-EM of amyloid fibrils and cellular aggregates Fitzpatrick, Anthony WP; Saibil, Helen R. Current Opinion in Structural Biology, Vol. 58 https://doi.org/10.1016/j.sbi.2019.05.003	journal	October 2019
Advances in cryo-electron tomography and subtomogram averaging and classification Zhang, Peijun Current Opinion in Structural Biology, Vol. 58 https://doi.org/10.1016/j.sbi.2019.05.021	journal	October 2019
Cryo-EM structures of tau filaments Scheres, Sjors HW; Zhang, Wenjuan; Falcon, Benjamin Current Opinion in Structural Biology, Vol. 64 https://doi.org/10.1016/j.sbi.2020.05.011	journal	October 2020
Multi-scale 3D Cryo-Correlative Microscopy for Vitrified Cells Wu, Gong-Her; Mitchell, Patrick G.; Galaz-Montoya, Jesus G. Structure, Vol. 28, Issue 11 https://doi.org/10.1016/j.str.2020.07.017	journal	November 2020
Quantifying Variability of Manual Annotation in Cryo-Electron Tomograms Hecksel, Corey W.; Darrow, Michele C.; Dai, Wei Microscopy and Microanalysis, Vol. 22, Issue 3 https://doi.org/10.1017/S1431927616000799	journal	May 2016
Proteins Containing Expanded Polyglutamine Tracts and Neurodegenerative Disease Adegbuyiro, Adewale; Sedighi, Faezeh; Pilkington, Albert W. Biochemistry, Vol. 56, Issue 9 https://doi.org/10.1021/acs.biochem.6b00936	journal	February 2017
Amyloid-like Features of Polyglutamine Aggregates and Their Assembly Kinetics ^† Chen, Songming; Berthelier, Valerie; Hamilton, J. Bradley Biochemistry, Vol. 41, Issue 23 https://doi.org/10.1021/bi011772q	journal	June 2002
Polyglutamine Amyloid Core Boundaries and Flanking Domain Dynamics in Huntingtin Fragment Fibrils Determined by Solid-State Nuclear Magnetic Resonance Hoop, Cody L.; Lin, Hsiang-Kai; Kar, Karunakar Biochemistry, Vol. 53, Issue 42 https://doi.org/10.1021/bi501010q	journal	October 2014
Super-Resolution Fluorescence of Huntingtin Reveals Growth of Globular Species into Short Fibers and Coexistence of Distinct Aggregates Duim, Whitney C.; Jiang, Yan; Shen, Koning ACS Chemical Biology, Vol. 9, Issue 12 https://doi.org/10.1021/cb500335w	journal	October 2014
Exploiting Amyloid Fibril Lamination for Nanotube Self-Assembly Lu, Kun; Jacob, Jaby; Thiyagarajan, Pappannan Journal of the American Chemical Society, Vol. 125, Issue 21 https://doi.org/10.1021/ja0341642	journal	May 2003
The Aggregation-Enhancing Huntingtin N-Terminus Is Helical in Amyloid Fibrils Sivanandam, V. N.; Jayaraman, Murali; Hoop, Cody L. Journal of the American Chemical Society, Vol. 133, Issue 12 https://doi.org/10.1021/ja110715f	journal	March 2011
Monomeric Huntingtin Exon 1 Has Similar Overall Structural Features for Wild-Type and Pathological Polyglutamine Lengths Warner, John B.; Ruff, Kiersten M.; Tan, Piau Siong Journal of the American Chemical Society, Vol. 139, Issue 41 https://doi.org/10.1021/jacs.7b06659	journal	October 2017
Towards a transgenic model of Huntington’s disease in a non-human primate Yang, Shang-Hsun; Cheng, Pei-Hsun; Banta, Heather Nature, Vol. 453, Issue 7197 https://doi.org/10.1038/nature06975	journal	May 2008
Cryo-EM structures of tau filaments from Alzheimer’s disease Fitzpatrick, Anthony W. P.; Falcon, Benjamin; He, Shaoda Nature, Vol. 547, Issue 7662 https://doi.org/10.1038/nature23002	journal	July 2017
Fibril polymorphism affects immobilized non-amyloid flanking domains of huntingtin exon1 rather than its polyglutamine core Lin, Hsiang-Kai; Boatz, Jennifer C.; Krabbendam, Inge E. Nature Communications, Vol. 8, Issue 1 https://doi.org/10.1038/ncomms15462	journal	May 2017
Convolutional neural networks for automated annotation of cellular cryo-electron tomograms Chen, Muyuan; Dai, Wei; Sun, Stella Y. Nature Methods, Vol. 14, Issue 10 https://doi.org/10.1038/nmeth.4405	journal	August 2017
Diseases of Unstable Repeat Expansion: Mechanisms and Common Principles Gatchel, Jennifer R.; Zoghbi, Huda Y. Nature Reviews Genetics, Vol. 6, Issue 10 https://doi.org/10.1038/nrg1691	journal	October 2005
Amyloid fibril structure of α-synuclein determined by cryo-electron microscopy Li, Yaowang; Zhao, Chunyu; Luo, Feng Cell Research, Vol. 28, Issue 9 https://doi.org/10.1038/s41422-018-0075-x	journal	July 2018
Cryo-EM of full-length α-synuclein reveals fibril polymorphs with a common structural kernel Li, Binsen; Ge, Peng; Murray, Kevin A. Nature Communications, Vol. 9, Issue 1 https://doi.org/10.1038/s41467-018-05971-2	journal	September 2018
A new era for understanding amyloid structures and disease Iadanza, Matthew G.; Jackson, Matthew P.; Hewitt, Eric W. Nature Reviews Molecular Cell Biology, Vol. 19, Issue 12 https://doi.org/10.1038/s41580-018-0060-8	journal	September 2018
Reducing effects of particle adsorption to the air–water interface in cryo-EM Noble, Alex J.; Wei, Hui; Dandey, Venkata P. Nature Methods, Vol. 15, Issue 10 https://doi.org/10.1038/s41592-018-0139-3	journal	September 2018
A complete data processing workflow for cryo-ET and subtomogram averaging Chen, Muyuan; Bell, James M.; Shi, Xiaodong Nature Methods, Vol. 16, Issue 11 https://doi.org/10.1038/s41592-019-0591-8	journal	October 2019
Conformational switch of polyglutamine-expanded huntingtin into benign aggregates leads to neuroprotective effect Sun, Chia-Sui; Lee, Chi-Chang; Li, Yi-Ni Scientific Reports, Vol. 5, Issue 1 https://doi.org/10.1038/srep14992	journal	October 2015
Nanoscale studies link amyloid maturity with polyglutamine diseases onset Ruggeri, F. S.; Vieweg, S.; Cendrowska, U. Scientific Reports, Vol. 6, Issue 1 https://doi.org/10.1038/srep31155	journal	August 2016
Distinct conformations of in vitro and in vivo amyloids of huntingtin-exon1 show different cytotoxicity Nekooki-Machida, Y.; Kurosawa, M.; Nukina, N. Proceedings of the National Academy of Sciences, Vol. 106, Issue 24 https://doi.org/10.1073/pnas.0812083106	journal	June 2009
Unmasking the roles of N- and C-terminal flanking sequences from exon 1 of huntingtin as modulators of polyglutamine aggregation Crick, S. L.; Ruff, K. M.; Garai, K. Proceedings of the National Academy of Sciences, Vol. 110, Issue 50 https://doi.org/10.1073/pnas.1320626110	journal	November 2013
Huntingtin exon 1 fibrils feature an interdigitated β-hairpin–based polyglutamine core Hoop, Cody L.; Lin, Hsiang-Kai; Kar, Karunakar Proceedings of the National Academy of Sciences, Vol. 113, Issue 6 https://doi.org/10.1073/pnas.1521933113	journal	February 2016
Molecular and structural architecture of polyQ aggregates in yeast Gruber, Anselm; Hornburg, Daniel; Antonin, Matthias Proceedings of the National Academy of Sciences, Vol. 115, Issue 15 https://doi.org/10.1073/pnas.1717978115	journal	March 2018
Self-assembly of polyglutamine-containing huntingtin fragments into amyloid-like fibrils: Implications for Huntington's disease pathology Scherzinger, E.; Sittler, A.; Schweiger, K. Proceedings of the National Academy of Sciences, Vol. 96, Issue 8 https://doi.org/10.1073/pnas.96.8.4604	journal	April 1999
Structural Features and Domain Organization of Huntingtin Fibrils Bugg, Charles W.; Isas, J. Mario; Fischer, Torsten Journal of Biological Chemistry, Vol. 287, Issue 38 https://doi.org/10.1074/jbc.M112.353839	journal	September 2012
Structural Mechanisms of Mutant Huntingtin Aggregation Suppression by the Synthetic Chaperonin-like CCT5 Complex Explained by Cryoelectron Tomography Darrow, Michele C.; Sergeeva, Oksana A.; Isas, Jose M. Journal of Biological Chemistry, Vol. 290, Issue 28 https://doi.org/10.1074/jbc.M115.655373	journal	May 2015
An Intein-based Strategy for the Production of Tag-free Huntingtin Exon 1 Proteins Enables New Insights into the Polyglutamine Dependence of Httex1 Aggregation and Fibril Formation Vieweg, Sophie; Ansaloni, Annalisa; Wang, Zhe-Ming Journal of Biological Chemistry, Vol. 291, Issue 23 https://doi.org/10.1074/jbc.M116.713982	journal	March 2016
Huntingtin Spheroids and Protofibrils as Precursors in Polyglutamine Fibrilization Poirier, Michelle A.; Li, Huilin; Macosko, Jed Journal of Biological Chemistry, Vol. 277, Issue 43 https://doi.org/10.1074/jbc.M205809200	journal	October 2002
Aggregated polyglutamine peptides delivered to nuclei are toxic to mammalian cells Yang, W. Human Molecular Genetics, Vol. 11, Issue 23 https://doi.org/10.1093/hmg/11.23.2905	journal	November 2002
Transgenic rat model of Huntington's disease von Horsten, S.; Schmitt, I.; Nguyen, H. P. Human Molecular Genetics, Vol. 12, Issue 6 https://doi.org/10.1093/hmg/ddg075	journal	March 2003
Suppression of polyglutamine-induced toxicity in cell and animal models of Huntington's disease by ubiquilin Wang, Hongmin; Lim, Precious J.; Yin, Chaobo Human Molecular Genetics, Vol. 15, Issue 6 https://doi.org/10.1093/hmg/ddl017	journal	February 2006
Identical oligomeric and fibrillar structures captured from the brains of R6/2 and knock-in mouse models of Huntington's disease Sathasivam, Kirupa; Lane, Amin; Legleiter, Justin Human Molecular Genetics, Vol. 19, Issue 1 https://doi.org/10.1093/hmg/ddp467	journal	October 2009
The huntingtin N17 domain is a multifunctional CRM1 and Ran-dependent nuclear and cilial export signal Maiuri, T.; Woloshansky, T.; Xia, J. Human Molecular Genetics, Vol. 22, Issue 7 https://doi.org/10.1093/hmg/dds554	journal	January 2013
The structural basis of protein folding and its links with human disease Dobson, Christopher M. Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences, Vol. 356, Issue 1406 https://doi.org/10.1098/rstb.2000.0758	journal	February 2001
Interference by Huntingtin and Atrophin-1 with CBP-Mediated Transcription Leading to Cellular Toxicity Nucifora Jr., F. C. Science, Vol. 291, Issue 5512 https://doi.org/10.1126/science.1056784	journal	March 2001
Aggregation of Huntingtin in Neuronal Intranuclear Inclusions and Dystrophic Neurites in Brain DiFiglia, Marian; Sapp, Ellen; Chase, Kathryn O. Science, Vol. 277, Issue 5334 https://doi.org/10.1126/science.277.5334.1990	journal	September 1997
Fibril structure of amyloid-β(1–42) by cryo–electron microscopy Gremer, Lothar; Schölzel, Daniel; Schenk, Carla Science, Vol. 358, Issue 6359 https://doi.org/10.1126/science.aao2825	journal	September 2017
Cryo-EM and Single Particles Wang, Liguo; Sigworth, Fred J. Physiology, Vol. 21, Issue 1 https://doi.org/10.1152/physiol.00045.2005	journal	February 2006
IPET and FETR: Experimental Approach for Studying Molecular Structure Dynamics by Cryo-Electron Tomography of a Single-Molecule Structure Zhang, Lei; Ren, Gang PLoS ONE, Vol. 7, Issue 1 https://doi.org/10.1371/journal.pone.0030249	journal	January 2012
TBK1 phosphorylates mutant Huntingtin and suppresses its aggregation and toxicity in Huntington's disease models Hegde, Ramanath Narayana; Chiki, Anass; Petricca, Lara The EMBO Journal, Vol. 39, Issue 17 https://doi.org/10.15252/embj.2020104671	journal	August 2020
Polyglutamine (PolyQ) Diseases: Genetics to Treatments Fan, Hueng-Chuen; Ho, Li-Ing; Chi, Ching-Shiang Cell Transplantation, Vol. 23, Issue 4-5 https://doi.org/10.3727/096368914X678454	journal	May 2014
TRiC’s tricks inhibit huntingtin aggregation Shahmoradian, Sarah H.; Galaz-Montoya, Jesus G.; Schmid, Michael F. eLife, Vol. 2 https://doi.org/10.7554/eLife.00710	journal	July 2013
Control of the structural landscape and neuronal proteotoxicity of mutant Huntingtin by domains flanking the polyQ tract Shen, Koning; Calamini, Barbara; Fauerbach, Jonathan A. eLife, Vol. 5 https://doi.org/10.7554/eLife.18065	journal	October 2016
Cryo-EM structure of alpha-synuclein fibrils Guerrero-Ferreira, Ricardo; Taylor, Nicholas MI; Mona, Daniel eLife, Vol. 7 https://doi.org/10.7554/eLife.36402	journal	July 2018

Similar Records

Secondary Structure of Huntingtin Amino-Terminal Region

Journal Article · Tue Sep 21 00:00:00 EDT 2010 · Structure · OSTI ID:1006178

Structural formation of huntingtin-like aggregates probed by small-angle neutron scattering

Journal Article · Fri Dec 31 23:00:00 EST 2010 · Biophysical Journal · OSTI ID:1014231

Rosiglitazone activation of PPARγ-dependent signaling is neuroprotective in mutant huntingtin expressing cells

Journal Article · Sun Nov 01 00:00:00 EDT 2015 · Experimental Cell Research · OSTI ID:22746373

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
cryoelectron tomography
protein aggregation

Cryo-electron tomography provides topological insights into mutant huntingtin exon 1 and polyQ aggregates

Citation Formats

References (81)

Similar Records

Related Subjects