{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T15:28:52Z","timestamp":1788276532028,"version":"build-2803163510"},"posted":{"date-parts":[[2026,8,25]]},"group-title":"Biophysics","reference-count":66,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["GM135158"],"award-info":[{"award-number":["GM135158"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["S10OD032253"],"award-info":[{"award-number":["S10OD032253"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Robert Champion Amyloidosis Research Fund","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Wildflower Foundation","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Italian Ministry of University and Research grant","award":["FIS00001548"],"award-info":[{"award-number":["FIS00001548"]}]},{"name":"Intramural Research Program NIDDK\/NIH"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,28]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Immunoglobulin light chain (LC) amyloidosis is a debilitating multiorgan disease with limited treatment options. Sequence and structural variability make LC amyloids particularly challenging for therapeutic targeting. We report four cryo-EM structures of \u03bb6-LC amyloid fibrils from four organs of two patients. Fibrils from different patients show different N-terminal conformations expanding known repertoire of \u03bb6-LC amyloid folds. These folds contain a planar \u03b2-arch with a flexible linker containing the complementarity-determining region 2, flanked by N- and C-terminal segments in variable patient-specific conformations. The surface location of the structurally frustrated charged segment may contribute to the overrepresentation of the \u03bb6-LC family in amyloidosis. These and other \u03bb6-LC amyloid structures from different patients show different side chain packing. Conversely, cardiac, renal and splenic amyloids from the same patient exhibit similar structures with small peripheral organ-specific variations. Moreover, they show similar \u201corphan\u201d densities, suggesting collagen-like triple helices bound to a tyrosine ladder along the fibril spine. Mass spectrometry detects collagen type-VI in tissue-extracted amyloids. Molecular dynamics simulations suggest amyloid binds collagen-VI triple helices via mixed interactions facilitated by the geometric complementarity between the layered amyloid structure and the triple helix. Similar interactions may drive formation of other amyloid-collagen complexes, influencing biological properties of amyloids.<\/jats:p>","DOI":"10.64898\/2026.08.24.746819","type":"posted-content","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T04:35:17Z","timestamp":1787718917000},"source":"Crossref","is-referenced-by-count":0,"title":["Cryo-EM reveals patient-\n                  <i>versus<\/i>\n                  organ-specific structural diversity and bound ligands in \u03bb6 light chain amyloids"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1088-608X","authenticated-orcid":false,"given":"Noorul","family":"Huda","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Physiology & Biophysics, Chobanian & Avedisian School of Medicine, Boston University, Boston, MA, 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