{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:52:49Z","timestamp":1786978369516,"version":"build-2736575974"},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,1,11]],"date-time":"2020-01-11T00:00:00Z","timestamp":1578700800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM078114"],"award-info":[{"award-number":["GM078114"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Islet amyloid polypeptide (IAPP), a 37 residue polypeptide, is the main protein component of islet amyloid deposits produced in the pancreas in Type 2 diabetes. Human IAPP contains five serine residues at positions 19, 20, 28, 29, and 34. Models of the IAPP amyloid fibril indicate a structure composed of two closely aligned columns of IAPP monomers with each monomer contributing to two intermolecular \u03b2\u2010strands. Ser 19 and Ser 20 are in the partially ordered \u03b2\u2010turn region, which links the two strands, whereas Ser 28, Ser 29, and Ser 34 are in the core region of the amyloid fibril. Ser 29 is involved in contacts between the two columns of monomers and is the part of the steric zipper interface. We undertook a study of individual serine substitutions with the hydrophobic isostere 2\u2010aminobutyric acid (2\u2010Abu) to examine the site\u2010specific role of serine side chains in IAPP amyloid formation. All five variants formed amyloid. The Ser 19 to 2\u2010Abu mutant accelerates amyloid formation by a factor of 3 to 4, while the Ser 29 to 2\u2010Abu mutation modestly slows the rate of amyloid formation. 2\u2010Abu replacements at the other sites had even smaller effects. The data demonstrate that the cross\u2010column interactions made by residue 29 are not essential for amyloid formation and also show that cross\u2010strand networks of hydrogen\u2010bonded Ser side chains, so called Ser\u2010ladders, are not required for IAPP amyloid formation. The effect of the Ser 19 to 2\u2010Abu mutant suggests that residues in this region are important for amyloid formation by IAPP.<\/jats:p>","DOI":"10.1002\/pro.3782","type":"journal-article","created":{"date-parts":[[2019,11,9]],"date-time":"2019-11-09T11:09:30Z","timestamp":1573297770000},"page":"555-563","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Differential effects of serine side chain interactions in amyloid formation by islet amyloid polypeptide"],"prefix":"10.1002","volume":"29","author":[{"given":"Rehana","family":"Akter","sequence":"first","affiliation":[{"name":"Department of Chemistry Stony Brook University  Stony Brook New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Chemistry Stony Brook University  Stony Brook New York"},{"name":"Laufer Center for Physical and Quantitative Biology Stony Brook University  Stony Brook New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3248-7493","authenticated-orcid":false,"given":"Daniel P.","family":"Raleigh","sequence":"additional","affiliation":[{"name":"Department of Chemistry Stony Brook University  Stony Brook New York"},{"name":"Laufer Center for Physical and Quantitative Biology Stony Brook University  Stony Brook New 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