{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T17:21:28Z","timestamp":1791825688230,"version":"4.3.4"},"reference-count":28,"publisher":"National Academy of Sciences","issue":"16","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,4,21]]},"abstract":"<jats:p>There is considerable interest in uncovering the pathway of amyloid formation because the toxic properties of amyloid likely stems from prefibril intermediates and not the fully formed fibrils. Using a recently invented method of collecting 2-dimensional infrared spectra and site-specific isotope labeling, we have measured the development of secondary structures for 6 residues during the aggregation process of the 37-residue polypeptide associated with type 2 diabetes, the human islet amyloid polypeptide (hIAPP). By monitoring the kinetics at 6 different labeled sites, we find that the peptides initially develop well-ordered structure in the region of the chain that is close to the ordered loop of the fibrils, followed by formation of the 2 parallel \u03b2-sheets with the N-terminal \u03b2-sheet likely forming before the C-terminal sheet. This experimental approach provides a detailed view of the aggregation pathway of hIAPP fibril formation as well as a general methodology for studying other amyloid forming proteins without the use of structure-perturbing labels.<\/jats:p>","DOI":"10.1073\/pnas.0805957106","type":"journal-article","created":{"date-parts":[[2009,4,3]],"date-time":"2009-04-03T22:43:05Z","timestamp":1238798585000},"page":"6614-6619","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":279,"title":["Two-dimensional IR spectroscopy and isotope labeling defines the pathway of amyloid formation with residue-specific resolution"],"prefix":"10.1073","volume":"106","author":[{"given":"Sang-Hee","family":"Shim","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Wisconsin, Madison, WI 53706-1396; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruchi","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Chemistry and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun L.","family":"Ling","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Wisconsin, Madison, WI 53706-1396; 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