{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:14:48Z","timestamp":1791328488816,"version":"4.3.1"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"9","license":[{"start":{"date-parts":[[2019,8,11]],"date-time":"2019-08-11T00:00:00Z","timestamp":1565481600000},"content-version":"vor","delay-in-days":181,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"name":"NIDDK, NIH","award":["DK029023"],"award-info":[{"award-number":["DK029023"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2019,2,26]]},"abstract":"<jats:p>\n                    The N-terminal region of the huntingtin protein, encoded by exon-1, comprises an amphiphilic domain (htt\n                    <jats:sup>NT<\/jats:sup>\n                    ), a polyglutamine (Q\n                    <jats:sub>\n                      <jats:italic>n<\/jats:italic>\n                    <\/jats:sub>\n                    ) tract, and a proline-rich sequence. Polyglutamine expansion results in an aggregation-prone protein responsible for Huntington\u2019s disease. Here, we study the earliest events involved in oligomerization of a minimalistic construct, htt\n                    <jats:sup>NT<\/jats:sup>\n                    Q\n                    <jats:sub>7<\/jats:sub>\n                    , which remains largely monomeric over a sufficiently long period of time to permit detailed quantitative NMR analysis of the kinetics and structure of sparsely populated\n                    <jats:inline-formula>\n                      <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" overflow=\"scroll\">\n                        <mml:mrow>\n                          <mml:mrow>\n                            <mml:mo>(<\/mml:mo>\n                            <mml:mrow>\n                              <mml:mi mathvariant=\"normal\">\u2272<\/mml:mi>\n                              <mml:mi mathvariant=\"bold\">2%<\/mml:mi>\n                            <\/mml:mrow>\n                            <mml:mo>)<\/mml:mo>\n                          <\/mml:mrow>\n                        <\/mml:mrow>\n                      <\/mml:math>\n                    <\/jats:inline-formula>\n                    oligomeric states, yet still eventually forms fibrils. Global fitting of concentration-dependent relaxation dispersion, transverse relaxation in the rotating frame, and exchange-induced chemical shift data reveals a bifurcated assembly mechanism in which the NMR observable monomeric species either self-associates to form a productive dimer (\u03c4\n                    <jats:sub>ex<\/jats:sub>\n                    \u223c 30 \u03bcs,\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>diss<\/jats:sub>\n                    \u223c 0.1 M) that goes on to form a tetramer (\n                    <jats:inline-formula>\n                      <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" overflow=\"scroll\">\n                        <mml:mrow>\n                          <mml:msub>\n                            <mml:mi mathvariant=\"bold\">\u03c4<\/mml:mi>\n                            <mml:mrow>\n                              <mml:mi mathvariant=\"bold\">ex<\/mml:mi>\n                            <\/mml:mrow>\n                          <\/mml:msub>\n                          <mml:mi mathvariant=\"normal\">\u2272<\/mml:mi>\n                          <mml:mi mathvariant=\"bold\">25<\/mml:mi>\n                        <\/mml:mrow>\n                      <\/mml:math>\n                    <\/jats:inline-formula>\n                    \u03bcs;\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>diss<\/jats:sub>\n                    \u223c 22 \u03bcM), or exchanges with a \u201cnonproductive\u201d dimer that does not oligomerize further (\u03c4\n                    <jats:sub>ex<\/jats:sub>\n                    \u223c 400 \u03bcs;\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>diss<\/jats:sub>\n                    \u223c 0.3 M). The excited state backbone chemical shifts are indicative of a contiguous helix (residues 3\u201317) in the productive dimer\/tetramer, with only partial helical character in the nonproductive dimer. A structural model of the productive dimer\/tetramer was obtained by simulated annealing driven by intermolecular paramagnetic relaxation enhancement data. The tetramer comprises a\n                    <jats:italic>D<\/jats:italic>\n                    <jats:sub>2<\/jats:sub>\n                    symmetric dimer of dimers with largely hydrophobic packing between the helical subunits. The structural model, validated by EPR distance measurements, illuminates the role of the htt\n                    <jats:sup>NT<\/jats:sup>\n                    domain in the earliest stages of prenucleation and oligomerization, before fibril formation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1821216116","type":"journal-article","created":{"date-parts":[[2019,2,11]],"date-time":"2019-02-11T20:40:46Z","timestamp":1549917646000},"page":"3562-3571","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":94,"title":["Probing initial transient oligomerization events facilitating Huntingtin fibril nucleation at atomic resolution by relaxation-based NMR"],"prefix":"10.1073","volume":"116","author":[{"given":"Samuel A.","family":"Kotler","sequence":"first","affiliation":[{"name":"Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitali","family":"Tugarinov","sequence":"additional","affiliation":[{"name":"Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Ceccon","sequence":"additional","affiliation":[{"name":"Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Libich","sequence":"additional","affiliation":[{"name":"Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodolfo","family":"Ghirlando","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0530;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles D.","family":"Schwieters","sequence":"additional","affiliation":[{"name":"Imaging Sciences Laboratory Center for Information Technology, National Institutes of Health, Bethesda, MD 20892-5624"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. Marius","family":"Clore","sequence":"additional","affiliation":[{"name":"Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2019,2,11]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1146\/annurev.neuro.29.051605.113042","article-title":"Trinucleotide repeat disorders","volume":"30","author":"Orr HT","year":"2007","unstructured":"HT Orr, HY Zoghbi, Trinucleotide repeat disorders. Annu Rev Neurosci 30, 575\u2013621 (2007).","journal-title":"Annu Rev Neurosci"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1152\/physrev.00041.2009","article-title":"Molecular mechanisms and potential therapeutical targets in Huntington\u2019s disease","volume":"90","author":"Zuccato C","year":"2010","unstructured":"C Zuccato, M Valenza, E Cattaneo, Molecular mechanisms and potential therapeutical targets in Huntington\u2019s disease. Physiol Rev 90, 905\u2013981 (2010).","journal-title":"Physiol Rev"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"15005","DOI":"10.1038\/nrdp.2015.5","article-title":"Huntington disease","volume":"1","author":"Bates GP","year":"2015","unstructured":"GP Bates, , Huntington disease. 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J Biol Chem 285, 8808\u20138823 (2010).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1073\/pnas.1221891110","article-title":"Aberrant splicing of HTT generates the pathogenic exon 1 protein in Huntington disease","volume":"110","author":"Sathasivam K","year":"2013","unstructured":"K Sathasivam, , Aberrant splicing of HTT generates the pathogenic exon 1 protein in Huntington disease. Proc Natl Acad Sci USA 110, 2366\u20132370 (2013).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/j.neuron.2016.02.003","article-title":"The biology of Huntingtin","volume":"89","author":"Saudou F","year":"2016","unstructured":"F Saudou, S Humbert, The biology of Huntingtin. Neuron 89, 910\u2013926 (2016).","journal-title":"Neuron"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/nsmb.1992","article-title":"Critical nucleus size for disease-related polyglutamine aggregation is repeat-length dependent","volume":"18","author":"Kar K","year":"2011","unstructured":"K Kar, M Jayaraman, B Sahoo, R Kodali, R Wetzel, Critical nucleus size for disease-related polyglutamine aggregation is repeat-length dependent. Nat Struct Mol Biol 18, 328\u2013336 (2011).","journal-title":"Nat Struct Mol Biol"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.celrep.2017.04.029","article-title":"Huntingtin inclusions trigger cellular quiescence, deactivate apoptosis, and lead to delayed necrosis","volume":"19","author":"Ramdzan YM","year":"2017","unstructured":"YM Ramdzan, , Huntingtin inclusions trigger cellular quiescence, deactivate apoptosis, and lead to delayed necrosis. Cell Rep 19, 919\u2013927 (2017).","journal-title":"Cell Rep"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"20075","DOI":"10.1073\/pnas.1320626110","article-title":"Unmasking the roles of N- and C-terminal flanking sequences from exon 1 of huntingtin as modulators of polyglutamine aggregation","volume":"110","author":"Crick SL","year":"2013","unstructured":"SL Crick, KM Ruff, K Garai, C Frieden, RV Pappu, Unmasking the roles of N- and C-terminal flanking sequences from exon 1 of huntingtin as modulators of polyglutamine aggregation. Proc Natl Acad Sci USA 110, 20075\u201320080 (2013).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"e18065","DOI":"10.7554\/eLife.18065","article-title":"Control of the structural landscape and neuronal proteotoxicity of mutant Huntingtin by domains flanking the polyQ tract","volume":"5","author":"Shen K","year":"2016","unstructured":"K Shen, , Control of the structural landscape and neuronal proteotoxicity of mutant Huntingtin by domains flanking the polyQ tract. eLife 5, e18065 (2016).","journal-title":"eLife"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.jmb.2011.06.045","article-title":"Structural characterization of polyglutamine fibrils by solid-state NMR spectroscopy","volume":"412","author":"Schneider R","year":"2011","unstructured":"R Schneider, , Structural characterization of polyglutamine fibrils by solid-state NMR spectroscopy. J Mol Biol 412, 121\u2013136 (2011).","journal-title":"J Mol Biol"},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"3942","DOI":"10.1021\/acs.biochem.5b00281","article-title":"Solid-state nuclear magnetic resonance on the static and dynamic domains of Huntingtin exon-1 fibrils","volume":"54","author":"Isas JM","year":"2015","unstructured":"JM Isas, R Langen, AB Siemer, Solid-state nuclear magnetic resonance on the static and dynamic domains of Huntingtin exon-1 fibrils. Biochemistry 54, 3942\u20133949 (2015).","journal-title":"Biochemistry"},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1073\/pnas.1521933113","article-title":"Huntingtin exon 1 fibrils feature an interdigitated \u03b2-hairpin-based polyglutamine core","volume":"113","author":"Hoop CL","year":"2016","unstructured":"CL Hoop, , Huntingtin exon 1 fibrils feature an interdigitated \u03b2-hairpin-based polyglutamine core. Proc Natl Acad Sci USA 113, 1546\u20131551 (2016).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"4558","DOI":"10.1021\/ja110715f","article-title":"The aggregation-enhancing huntingtin N-terminus is helical in amyloid fibrils","volume":"133","author":"Sivanandam VN","year":"2011","unstructured":"VN Sivanandam, , The aggregation-enhancing huntingtin N-terminus is helical in amyloid fibrils. J Am Chem Soc 133, 4558\u20134566 (2011).","journal-title":"J Am Chem Soc"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"6653","DOI":"10.1021\/bi501010q","article-title":"Polyglutamine amyloid core boundaries and flanking domain dynamics in huntingtin fragment fibrils determined by solid-state nuclear magnetic resonance","volume":"53","author":"Hoop CL","year":"2014","unstructured":"CL Hoop, , Polyglutamine amyloid core boundaries and flanking domain dynamics in huntingtin fragment fibrils determined by solid-state nuclear magnetic resonance. Biochemistry 53, 6653\u20136666 (2014).","journal-title":"Biochemistry"},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"15462","DOI":"10.1038\/ncomms15462","article-title":"Fibril polymorphism affects immobilized non-amyloid flanking domains of huntingtin exon1 rather than its polyglutamine core","volume":"8","author":"Lin H-K","year":"2017","unstructured":"H-K Lin, , Fibril polymorphism affects immobilized non-amyloid flanking domains of huntingtin exon1 rather than its polyglutamine core. Nat Commun 8, 15462 (2017).","journal-title":"Nat Commun"},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/j.cell.2010.11.042","article-title":"Essential role of coiled coils for aggregation and activity of Q\/N-rich prions and PolyQ proteins","volume":"143","author":"Fiumara F","year":"2010","unstructured":"F Fiumara, L Fioriti, ER Kandel, WA Hendrickson, Essential role of coiled coils for aggregation and activity of Q\/N-rich prions and PolyQ proteins. Cell 143, 1121\u20131135 (2010).","journal-title":"Cell"},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.jmb.2012.01.030","article-title":"Physical chemistry of polyglutamine: Intriguing tales of a monotonous sequence","volume":"421","author":"Wetzel R","year":"2012","unstructured":"R Wetzel, Physical chemistry of polyglutamine: Intriguing tales of a monotonous sequence. J Mol Biol 421, 466\u2013490 (2012).","journal-title":"J Mol Biol"},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.jmb.2011.12.010","article-title":"Slow amyloid nucleation via \u03b1-helix-rich oligomeric intermediates in short polyglutamine-containing huntingtin fragments","volume":"415","author":"Jayaraman M","year":"2012","unstructured":"M Jayaraman, , Slow amyloid nucleation via \u03b1-helix-rich oligomeric intermediates in short polyglutamine-containing huntingtin fragments. J Mol Biol 415, 881\u2013899 (2012).","journal-title":"J Mol Biol"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"3623","DOI":"10.1021\/cr030413t","article-title":"NMR characterization of the dynamics of biomacromolecules","volume":"104","author":"Palmer AG","year":"2004","unstructured":"3rd AG Palmer, NMR characterization of the dynamics of biomacromolecules. Chem Rev 104, 3623\u20133640 (2004).","journal-title":"Chem Rev"},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1126\/science.1124964","article-title":"New tools provide new insights in NMR studies of protein dynamics","volume":"312","author":"Mittermaier A","year":"2006","unstructured":"A Mittermaier, LE Kay, New tools provide new insights in NMR studies of protein dynamics. Science 312, 224\u2013228 (2006).","journal-title":"Science"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1021\/cr0404287","article-title":"Characterization of the dynamics of biomacromolecules using rotating-frame spin relaxation NMR spectroscopy","volume":"106","author":"Palmer AG","year":"2006","unstructured":"3rd AG Palmer, F Massi, Characterization of the dynamics of biomacromolecules using rotating-frame spin relaxation NMR spectroscopy. Chem Rev 106, 1700\u20131719 (2006).","journal-title":"Chem Rev"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","first-page":"14891","DOI":"10.1021\/jp209610v","article-title":"Increasing the exchange time-scale that can be probed by CPMG relaxation dispersion NMR","volume":"115","author":"Vallurupalli P","year":"2011","unstructured":"P Vallurupalli, G Bouvignies, LE Kay, Increasing the exchange time-scale that can be probed by CPMG relaxation dispersion NMR. J Phys Chem B 115, 14891\u201314900 (2011).","journal-title":"J Phys Chem B"},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.jmr.2006.10.003","article-title":"Practical aspects of 1H transverse paramagnetic relaxation enhancement measurements on macromolecules","volume":"184","author":"Iwahara J","year":"2007","unstructured":"J Iwahara, C Tang, G Marius Clore, Practical aspects of 1H transverse paramagnetic relaxation enhancement measurements on macromolecules. J Magn Reson 184, 185\u2013195 (2007).","journal-title":"J Magn Reson"},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"4108","DOI":"10.1021\/cr900033p","article-title":"Theory, practice, and applications of paramagnetic relaxation enhancement for the characterization of transient low-population states of biological macromolecules and their complexes","volume":"109","author":"Clore GM","year":"2009","unstructured":"GM Clore, J Iwahara, Theory, practice, and applications of paramagnetic relaxation enhancement for the characterization of transient low-population states of biological macromolecules and their complexes. Chem Rev 109, 4108\u20134139 (2009).","journal-title":"Chem Rev"},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1146\/annurev-physchem-032511-143716","article-title":"DEER distance measurements on proteins","volume":"63","author":"Jeschke G","year":"2012","unstructured":"G Jeschke, DEER distance measurements on proteins. Annu Rev Phys Chem 63, 419\u2013446 (2012).","journal-title":"Annu Rev Phys Chem"},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/bs.mie.2015.08.006","article-title":"Exploring structure, dynamics, and topology of nitroxide spin-labeled proteins using continuous-wave electron paramagnetic resonance spectroscopy","volume":"564","author":"Altenbach C","year":"2015","unstructured":"C Altenbach, CJ L\u00f3pez, K Hideg, WL Hubbell, Exploring structure, dynamics, and topology of nitroxide spin-labeled proteins using continuous-wave electron paramagnetic resonance spectroscopy. Methods Enzymol 564, 59\u2013100 (2015).","journal-title":"Methods Enzymol"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"29427","DOI":"10.1074\/jbc.M109.013193","article-title":"Phosphorylation of threonine 3: Implications for Huntingtin aggregation and neurotoxicity","volume":"284","author":"Aiken CT","year":"2009","unstructured":"CT Aiken, , Phosphorylation of threonine 3: Implications for Huntingtin aggregation and neurotoxicity. J Biol Chem 284, 29427\u201329436 (2009).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1017\/S0033583514000122","article-title":"Visualizing transient dark states by NMR spectroscopy","volume":"48","author":"Anthis NJ","year":"2015","unstructured":"NJ Anthis, GM Clore, Visualizing transient dark states by NMR spectroscopy. Q Rev Biophys 48, 35\u2013116 (2015).","journal-title":"Q Rev Biophys"},{"key":"e_1_3_4_30_2","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/nature10577","article-title":"Atomic-resolution dynamics on the surface of amyloid-\u03b2 protofibrils probed by solution NMR","volume":"480","author":"Fawzi NL","year":"2011","unstructured":"NL Fawzi, J Ying, R Ghirlando, DA Torchia, GM Clore, Atomic-resolution dynamics on the surface of amyloid-\u03b2 protofibrils probed by solution NMR. Nature 480, 268\u2013272 (2011).","journal-title":"Nature"},{"key":"e_1_3_4_31_2","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1063\/1.1744152","article-title":"Reaction rates by nuclear magnetic resonance","volume":"28","author":"McConnell HM","year":"1958","unstructured":"HM McConnell, Reaction rates by nuclear magnetic resonance. J Chem Phys 28, 430\u2013431 (1958).","journal-title":"J Chem Phys"},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1021\/acs.biochem.6b01263","article-title":"Self-assembly of human Profilin-1 detected by Carr\u2013Purcell\u2013Meiboom\u2013Gill nuclear magnetic resonance (CPMG NMR) spectroscopy","volume":"56","author":"Rennella E","year":"2017","unstructured":"E Rennella, A Sekhar, LE Kay, Self-assembly of human Profilin-1 detected by Carr\u2013Purcell\u2013Meiboom\u2013Gill nuclear magnetic resonance (CPMG NMR) spectroscopy. Biochemistry 56, 692\u2013703 (2017).","journal-title":"Biochemistry"},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s10858-009-9333-z","article-title":"TALOS+: A hybrid method for predicting protein backbone torsion angles from NMR chemical shifts","volume":"44","author":"Shen Y","year":"2009","unstructured":"Y Shen, F Delaglio, G Cornilescu, A Bax, TALOS+: A hybrid method for predicting protein backbone torsion angles from NMR chemical shifts. J Biomol NMR 44, 213\u2013223 (2009).","journal-title":"J Biomol NMR"},{"key":"e_1_3_4_34_2","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/978-1-4939-2239-0_2","article-title":"Protein structural information derived from NMR chemical shift with the neural network program TALOS-N","volume":"1260","author":"Shen Y","year":"2015","unstructured":"Y Shen, A Bax, Protein structural information derived from NMR chemical shift with the neural network program TALOS-N. Methods Mol Biol 1260, 17\u201332 (2015).","journal-title":"Methods Mol Biol"},{"key":"e_1_3_4_35_2","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.pnmrs.2005.10.001","article-title":"Using Xplor-NIH for NMR molecular structure determination","volume":"48","author":"Schwieters CD","year":"2006","unstructured":"CD Schwieters, JJ Kuszewski, GM Clore, Using Xplor-NIH for NMR molecular structure determination. Prog Nucl Magn Reson Spectrosc 48, 47\u201362 (2006).","journal-title":"Prog Nucl Magn Reson Spectrosc"},{"key":"e_1_3_4_36_2","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1002\/pro.3248","article-title":"Xplor-NIH for molecular structure determination from NMR and other data sources","volume":"27","author":"Schwieters CD","year":"2018","unstructured":"CD Schwieters, GA Bermejo, GM Clore, Xplor-NIH for molecular structure determination from NMR and other data sources. Protein Sci 27, 26\u201340 (2018).","journal-title":"Protein Sci"},{"key":"e_1_3_4_37_2","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/nsb0495-321","article-title":"Refined solution structure of the oligomerization domain of the tumour suppressor p53","volume":"2","author":"Clore GM","year":"1995","unstructured":"GM Clore, , Refined solution structure of the oligomerization domain of the tumour suppressor p53. Nat Struct Biol 2, 321\u2013333 (1995).","journal-title":"Nat Struct Biol"},{"key":"e_1_3_4_38_2","doi-asserted-by":"crossref","first-page":"2987","DOI":"10.1002\/cphc.201600726","article-title":"Quantitative resolution of monomer-dimer populations by inversion modulated DEER EPR spectroscopy","volume":"17","author":"Schmidt T","year":"2016","unstructured":"T Schmidt, R Ghirlando, J Baber, GM Clore, Quantitative resolution of monomer-dimer populations by inversion modulated DEER EPR spectroscopy. ChemPhysChem 17, 2987\u20132991 (2016).","journal-title":"ChemPhysChem"},{"key":"e_1_3_4_39_2","doi-asserted-by":"crossref","first-page":"6199","DOI":"10.1021\/jacs.8b02619","article-title":"Interaction of Huntingtin exon-1 peptides withl lipid-based micellar nanoparticles probed by solution NMR and Q-band pulsed EPR","volume":"140","author":"Ceccon A","year":"2018","unstructured":"A Ceccon, , Interaction of Huntingtin exon-1 peptides withl lipid-based micellar nanoparticles probed by solution NMR and Q-band pulsed EPR. J Am Chem Soc 140, 6199\u20136202 (2018).","journal-title":"J Am Chem Soc"},{"key":"e_1_3_4_40_2","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/BF03166213","article-title":"DeerAnalysis2006\u2013A comprehensive software package for analyzing pulsed ELDOR data","volume":"30","author":"Jeschke G","year":"2006","unstructured":"G Jeschke, , DeerAnalysis2006\u2013A comprehensive software package for analyzing pulsed ELDOR data. Appl Magn Reson 30, 473\u2013498 (2006).","journal-title":"Appl Magn Reson"},{"key":"e_1_3_4_41_2","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1515\/bmc-2015-0001","article-title":"The emerging role of the first 17 amino acids of huntingtin in Huntington\u2019s disease","volume":"6","author":"Arndt JR","year":"2015","unstructured":"JR Arndt, M Chaibva, J Legleiter, The emerging role of the first 17 amino acids of huntingtin in Huntington\u2019s disease. Biomol Concepts 6, 33\u201346 (2015).","journal-title":"Biomol Concepts"},{"key":"e_1_3_4_42_2","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1021\/jacs.6b10893","article-title":"Structure and dynamics of the Huntingtin exon-1 N-terminus: A solution NMR perspective","volume":"139","author":"Baias M","year":"2017","unstructured":"M Baias, , Structure and dynamics of the Huntingtin exon-1 N-terminus: A solution NMR perspective. J Am Chem Soc 139, 1168\u20131176 (2017).","journal-title":"J Am Chem Soc"},{"key":"e_1_3_4_43_2","doi-asserted-by":"crossref","first-page":"2597","DOI":"10.1074\/jbc.M117.813667","article-title":"The 17-residue-long N terminus in huntingtin controls stepwise aggregation in solution and on membranes via different mechanisms","volume":"293","author":"Pandey NK","year":"2018","unstructured":"NK Pandey, , The 17-residue-long N terminus in huntingtin controls stepwise aggregation in solution and on membranes via different mechanisms. J Biol Chem 293, 2597\u20132605 (2018).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_44_2","doi-asserted-by":"crossref","first-page":"19613","DOI":"10.1074\/jbc.RA118.004808","article-title":"The folding equilibrium of huntingtin exon 1 monomer depends on its polyglutamine tract","volume":"293","author":"Bravo-Arredondo JM","year":"2018","unstructured":"JM Bravo-Arredondo, , The folding equilibrium of huntingtin exon 1 monomer depends on its polyglutamine tract. J Biol Chem 293, 19613\u201319623 (2018).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_45_2","volume-title":"Biophysical Chemistry Part III: The Behavior of Biological Macromolcules","author":"Cantor CR","year":"1980","unstructured":"CR Cantor, PR Schimmel Biophysical Chemistry Part III: The Behavior of Biological Macromolcules (Freeman, San Francisco, 1980)."},{"key":"e_1_3_4_46_2","doi-asserted-by":"crossref","first-page":"5879","DOI":"10.1021\/ja031580d","article-title":"Ensemble approach for NMR structure refinement against 1H paramagnetic relaxation enhancement data arising from a flexible paramagnetic group attached to a macromolecule","volume":"126","author":"Iwahara J","year":"2004","unstructured":"J Iwahara, CD Schwieters, GM Clore, Ensemble approach for NMR structure refinement against 1H paramagnetic relaxation enhancement data arising from a flexible paramagnetic group attached to a macromolecule. J Am Chem Soc 126, 5879\u20135896 (2004).","journal-title":"J Am Chem Soc"},{"key":"e_1_3_4_47_2","unstructured":"SA Kotler Structure of the Huttingtin tetramer\/dimer mixture determined by paramagnetic NMR. Protein Data Bank. Available at https:\/\/www.rcsb.org\/structure\/6N8C. Deposited November 30 2018. (2018)."},{"key":"e_1_3_4_48_2","unstructured":"SA Kotler Structure of the Huttingtin tetramer\/dimer mixture determined by paramagnetic NMR. Biological Magnetic Resonance Data Bank. Available at http:\/\/www.bmrb.wisc.edu\/data_library\/summary\/index.php?bmrbId=30545. Deposited December 6 2018. 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