{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T04:37:41Z","timestamp":1776400661696,"version":"3.51.2"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1009833","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T00:00:00Z","timestamp":1645747200000}}],"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T00:00:00Z","timestamp":1644796800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1724300"],"award-info":[{"award-number":["1724300"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"name":"VW Foundation","award":["#94747"],"award-info":[{"award-number":["#94747"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    As sequence and structure comparison algorithms gain sensitivity, the intrinsic interconnectedness of the protein universe has become increasingly apparent. Despite this general trend, \u03b2-trefoils have emerged as an uncommon counterexample: They are an isolated protein lineage for which few, if any, sequence or structure associations to other lineages have been identified. If \u03b2-trefoils are, in fact, remote islands in sequence-structure space, it implies that the oligomerizing peptide that founded the \u03b2-trefoil lineage itself arose\n                    <jats:italic>de novo<\/jats:italic>\n                    . To better understand \u03b2-trefoil evolution, and to probe the limits of fragment sharing across the protein universe, we identified both \u2018\u03b2-trefoil bridging themes\u2019 (evolutionarily-related sequence segments) and \u2018\u03b2-trefoil-like motifs\u2019 (structure motifs with a hallmark feature of the \u03b2-trefoil architecture) in multiple, ostensibly unrelated, protein lineages. The success of the present approach stems, in part, from considering \u03b2-trefoil sequence segments or structure motifs rather than the \u03b2-trefoil architecture as a whole, as has been done previously. The newly uncovered inter-lineage connections presented here suggest a novel hypothesis about the origins of the \u03b2-trefoil fold itself\u2013namely, that it is a derived fold formed by \u2018budding\u2019 from an Immunoglobulin-like \u03b2-sandwich protein. These results demonstrate how the evolution of a folded domain from a peptide need not be a signature of antiquity and underpin an emerging truth: few protein lineages escape nature\u2019s sewing table.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1009833","type":"journal-article","created":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T13:59:00Z","timestamp":1644847140000},"page":"e1009833","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["Evidence for the emergence of \u03b2-trefoils by \u2018Peptide Budding\u2019 from an IgG-like \u03b2-sandwich"],"prefix":"10.1371","volume":"18","author":[{"given":"Liam M.","family":"Longo","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8523-1614","authenticated-orcid":true,"given":"Rachel","family":"Kolodny","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8199-7011","authenticated-orcid":true,"given":"Shawn E.","family":"McGlynn","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2022,2,14]]},"reference":[{"key":"pcbi.1009833.ref001","article-title":"Structural Bridges through Fold Space","author":"H Edwards","year":"2015","journal-title":"PLoS Computational Biology"},{"key":"pcbi.1009833.ref002","first-page":"14","article-title":"Loop fold nature of globular proteins","author":"IN Berezovsky","year":"2001","journal-title":"Protein Engineering"},{"key":"pcbi.1009833.ref003","doi-asserted-by":"crossref","unstructured":"Nepomnyachiy S, Ben-Tal N, Kolodny R. 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