{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T00:28:14Z","timestamp":1786753694368,"version":"build-2736575974"},"posted":{"date-parts":[[2026,8,12]]},"group-title":"Microbiology","reference-count":70,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Intrinsic protein disorder plays a central role in cellular regulation and host-pathogen interactions, yet its proteome-wide distribution and functional organization in amoebozoan parasites remain poorly understood. Here, we present the first comparative analysis of intrinsic disorder across the proteomes of\n                  <jats:italic>Entamoeba histolytica<\/jats:italic>\n                  , which causes amoebic dysentery, and two related species,\n                  <jats:italic>E. dispar<\/jats:italic>\n                  , and\n                  <jats:italic>E. invadens<\/jats:italic>\n                  . For comparison, we analyzed intrinsic protein disorder in two phylogenetically distant parasites,\n                  <jats:italic>Plasmodium falciparum<\/jats:italic>\n                  and\n                  <jats:italic>Trypanosoma brucei<\/jats:italic>\n                  . Overall,\n                  <jats:italic>Entamoeba<\/jats:italic>\n                  species exhibited significantly lower levels of intrinsic disorder than\n                  <jats:italic>P. falciparum<\/jats:italic>\n                  and\n                  <jats:italic>T. brucei<\/jats:italic>\n                  . Despite this, all organisms displayed a conserved functional trend in which increasing disorder was associated with a shift from metabolic and catalytic processes toward gene expression-related functions. However, notable organism-specific differences emerged.\n                  <jats:italic>P. falciparum<\/jats:italic>\n                  showed persistent enrichment of gene expression functions across all disorder levels, while\n                  <jats:italic>T. brucei<\/jats:italic>\n                  maintained metabolic, redox, and transport processes throughout the disorder spectrum. In contrast,\n                  <jats:italic>Entamoeba<\/jats:italic>\n                  species uniquely retained GTPase- and phosphorylation-associated signaling across all levels of disorder, with the strongest enrichment observed in the pathogenic species,\n                  <jats:italic>E. histolytica<\/jats:italic>\n                  and\n                  <jats:italic>E. invadens<\/jats:italic>\n                  . This pattern likely reflects a reliance on rapid environmental sensing, cytoskeletal remodeling, and vesicle trafficking, necessary for successful infection. Consistent with this, there was reduced enrichment of G-protein signaling in the non-pathogenic commensal,\n                  <jats:italic>E. dispar<\/jats:italic>\n                  , especially in highly disordered proteins. Secretome analysis further revealed that, unlike\n                  <jats:italic>P. falciparum<\/jats:italic>\n                  ,\n                  <jats:italic>E. histolytica<\/jats:italic>\n                  possesses a more structurally ordered secretome, suggesting selection for stable catalytic proteins in the host intestinal environment. Finally, no consistent relationship was identified between intrinsic disorder and vaccine efficacy for several key antigenic targets. Together, these findings demonstrate that intrinsic disorder is differentially deployed across parasites, and utilization of disordered proteins has diverged in accordance with each organism\u2019s lifecycle and host interaction strategy. These findings highlight the role of intrinsic disorder in shaping parasitism.\n                <\/jats:p>","DOI":"10.64898\/2026.08.12.744381","type":"posted-content","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T03:30:15Z","timestamp":1786591815000},"source":"Crossref","is-referenced-by-count":0,"title":["Intrinsic protein disorder reveals divergent signaling architectures and lifestyle adaptation in\n                  <i>Entamoeba<\/i>\n                  species"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9992-5198","authenticated-orcid":false,"given":"Rooksana E.","family":"Noorai","sequence":"first","affiliation":[{"name":"Clemson University Genomics and Bioinformatics Facility (CUGBF), Clemson, SC 29634"},{"name":"Research Computing and Data, Clemson University, Clemson, SC 29634"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9662-5501","authenticated-orcid":false,"given":"Stevin","family":"Wilson","sequence":"additional","affiliation":[{"name":"Clemson University Genomics and Bioinformatics Facility (CUGBF), Clemson, SC 29634"},{"name":"Illumina, Inc., San Diego, CA 92122"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4154-8158","authenticated-orcid":false,"given":"Lesly A.","family":"Temesvari","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Clemson University, Clemson, SC 29634"},{"name":"Eukaryotic Pathogens Innovation Center (EPIC), Clemson University, Clemson, SC 29634"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026081417000647000_2026.08.12.744381v1.1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232214050"},{"key":"2026081417000647000_2026.08.12.744381v1.2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R115.685859"},{"key":"2026081417000647000_2026.08.12.744381v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/bs.pmbts.2020.03.001"},{"key":"2026081417000647000_2026.08.12.744381v1.4","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2012.675145"},{"key":"2026081417000647000_2026.08.12.744381v1.5","article-title":"Unstructured but dangerous-the emerging roles of intrinsically disordered protein regions in bacterial pathogenesis","year":"2026","journal-title":"FEBS Lett"},{"key":"2026081417000647000_2026.08.12.744381v1.6","doi-asserted-by":"publisher","DOI":"10.1080\/21690707.2015.1135015"},{"key":"2026081417000647000_2026.08.12.744381v1.7","doi-asserted-by":"publisher","DOI":"10.4161\/idp.24360"},{"key":"2026081417000647000_2026.08.12.744381v1.8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0053785"},{"key":"2026081417000647000_2026.08.12.744381v1.9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006552"},{"key":"2026081417000647000_2026.08.12.744381v1.10","doi-asserted-by":"crossref","first-page":"e1012186","DOI":"10.1371\/journal.ppat.1012186","article-title":"Beyond the VSG layer: Exploring the role of intrinsic disorder in the invariant surface glycoproteins of African trypanosomes","volume":"20","year":"2024","journal-title":"PLoS Pathog"},{"key":"2026081417000647000_2026.08.12.744381v1.11","doi-asserted-by":"crossref","first-page":"e0141729","DOI":"10.1371\/journal.pone.0141729","article-title":"Insights into the immunological properties of intrinsically disordered malaria proteins using proteome scale predictions","volume":"10","year":"2015","journal-title":"PLoS One"},{"issue":"144158","key":"2026081417000647000_2026.08.12.744381v1.12","article-title":"Proteome-wide identification and comprehensive profiling of intrinsic disorder in Fasciola gigantica","volume":"314","year":"2025","journal-title":"Int J Biol Macromol"},{"key":"2026081417000647000_2026.08.12.744381v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2006.08.011"},{"key":"2026081417000647000_2026.08.12.744381v1.14","doi-asserted-by":"publisher","DOI":"10.1039\/c3mb25517d"},{"key":"2026081417000647000_2026.08.12.744381v1.15","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.03412-23"},{"key":"2026081417000647000_2026.08.12.744381v1.16","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1186\/1471-2164-15-1100","article-title":"Intrinsically disordered proteins (IDPs) in trypanosomatids","volume":"15","year":"2014","journal-title":"BMC Genomics"},{"key":"2026081417000647000_2026.08.12.744381v1.17","unstructured":"Chou A , Austin RL. 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