{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T10:30:52Z","timestamp":1791023452270,"version":"4.1.0"},"reference-count":17,"publisher":"National Academy of Sciences","issue":"8","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,4,16]]},"abstract":"<jats:p>\n                    A study of papers on amyloid fibers suggested to us that cylindrical \u03b2-sheets are the only structures consistent with some of the x-ray and electron microscope data. We then found that our own 7-year-old and hitherto enigmatic x-ray diagram of poly-\n                    <jats:sc>l<\/jats:sc>\n                    -glutamine fits a cylindrical sheet of 31 \u212b diameter made of \u03b2-strands with 20 residues per helical turn. Successive turns are linked by hydrogen bonds between both the main chain and side chain amides, and side chains point alternately into and out of the cylinder. Fibers of the exon-1 peptide of huntingtin and of the glutamine- and asparagine-rich region of the yeast prion Sup35 give the same underlying x-ray diagrams, which show that they have the same structure. Electron micrographs show that the 100-\u212b-thick fibers of the Sup35 peptide are ropes made of three protofibrils a little over 30 \u212b thick. They have a measured mass of 1,450 Da\/\u212b, compared with 1,426 Da\/\u212b for a calculated mass of three protofibrils each with 20 residues per helical turn wound around each other with a helical pitch of 510 \u212b. Published x-ray diagrams and electron micrographs show that fibers of synuclein, the protein that forms the aggregates of Parkinson disease, consist of single cylindrical \u03b2-sheets. Fibers of Alzheimer A\u03b2 fragments and variants are probably made of either two or three concentric cylindrical \u03b2-sheets. Our structure of poly-\n                    <jats:sc>l<\/jats:sc>\n                    -glutamine fibers may explain why, in all but one of the neurodegenerative diseases resulting from extension of glutamine repeats, disease occurs when the number of repeats exceeds 37\u201340. A single helical turn with 20 residues would be unstable, because there is nothing to hold it in place, but two turns with 40 residues are stabilized by the hydrogen bonds between their amides and can act as nuclei for further helical growth. The A\u03b2 peptide of Alzheimer's disease contains 42 residues, the best number for nucleating further growth. All these structures are very stable; the best hope for therapies lies in preventing their growth.\n                  <\/jats:p>","DOI":"10.1073\/pnas.042681399","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:45:09Z","timestamp":1027680309000},"page":"5591-5595","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":450,"title":["Amyloid fibers are water-filled nanotubes"],"prefix":"10.1073","volume":"99","author":[{"given":"M. F.","family":"Perutz","sequence":"first","affiliation":[{"name":"Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 2QH, United Kingdom; and Department of Haematology, University of Cambridge, Wellcome\/MRC Building, Cambridge CB2 2XY, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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Press, Oxford Glutamine Repeats and Neurodegenerative Diseases: Molecular Aspects, 2001)."},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80514-0"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/35039051"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/35084141"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.042681599"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/35086601"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2000.0766"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","unstructured":"Yamamoto A. Lucas J. J. & Hen R. 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