{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:03:25Z","timestamp":1788498205618,"version":"build-2803163510"},"reference-count":79,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T00:00:00Z","timestamp":1721088000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK13221401"],"award-info":[{"award-number":["DK13221401"]}],"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":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Despite causing over 1\u2009million deaths annually, Type 2 Diabetes (T2D) currently has no curative treatments. Aggregation of the islet amyloid polypeptide (hIAPP) into amyloid plaques plays an important role in the pathophysiology of T2D and thus presents a target for therapeutic intervention. The mechanism by which hIAPP aggregates contribute to the development of T2D is unclear, but it is proposed to involve disruption of cellular membranes. However, nearly all research on hIAPP\u2010lipid interactions has focused on anionic phospholipids, which are primarily present in the cytosolic face of plasma membranes. We seek here to characterize the effects of three gangliosides, the dominant anionic lipids in the outer leaflet of the plasma membrane, on the aggregation, structure, and toxicity of hIAPP. Our results show a dual behavior that depends on the molar ratio between the gangliosides and hIAPP. For each ganglioside, a low\u2010lipid:peptide ratio enhances hIAPP aggregation and alters the morphology of hIAPP fibrils, while a high ratio eliminates aggregation and stabilizes an\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010helix\u2010rich hIAPP conformation. A more negative lipid charge more efficiently promotes aggregation, and a larger lipid headgroup improves inhibition of aggregation. hIAPP also alters the phase transitions of the lipids, favoring spherical micelles over larger tubular micelles. We discuss our results in the context of the available lipid surface area for hIAPP binding and speculate on a role for gangliosides in facilitating toxic hIAPP aggregation.\n                  <\/jats:p>","DOI":"10.1002\/pro.5119","type":"journal-article","created":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T08:05:52Z","timestamp":1721117152000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Differential effects of ganglioside lipids on the conformation and aggregation of islet amyloid polypeptide"],"prefix":"10.1002","volume":"33","author":[{"given":"Samuel D.","family":"McCalpin","sequence":"first","affiliation":[{"name":"Biophysics Program University of Michigan  Ann Arbor Michigan USA"},{"name":"Department of Chemistry University of Michigan  Ann Arbor Michigan 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Chemistry University of Michigan  Ann Arbor Michigan USA"},{"name":"Michigan Neuroscience Institute University of Michigan  Ann Arbor Michigan USA"},{"name":"Biomedical Engineering, Macromolecular Science and Engineering University of Michigan  Ann Arbor Michigan USA"},{"name":"National High Magnetic Field Laboratory, Department of Chemical and Biomedical Engineering, Institute of Molecular Biophysics, Neuroscience Florida State University  Tallahassee Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI85210"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.12977"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M801383200"},{"issue":"4","key":"e_1_2_7_5_1","first-page":"879","article-title":"Aggregation of alpha\u2010synuclein in Lewy bodies of sporadic Parkinson's disease and 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