{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T13:38:05Z","timestamp":1786541885128,"version":"build-2736575974"},"reference-count":65,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000015","name":"U.S. Department of Energy","doi-asserted-by":"crossref","award":["DE-FC02-02ER63421"],"award-info":[{"award-number":["DE-FC02-02ER63421"]}],"id":[{"id":"10.13039\/100000015","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01-AI161828"],"award-info":[{"award-number":["R01-AI161828"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"HHS | National Institutes of Health","award":["T32GM145388"],"award-info":[{"award-number":["T32GM145388"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2026,8,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Cellulosomes are large, surface-displayed enzyme complexes that enable anaerobic bacteria to degrade recalcitrant plant polysaccharides, yet cellulosome-expressing bacteria are thought to be rare in the human gut. Here, we show that extensive sequence divergence obscures the detection of many ruminococcal cellulosomes by conventional sequence homology-based methods. Using proteome-scale AlphaFold2 structural predictions, we uncovered a substantially expanded set of putative cellulosome-producing\n                      <jats:italic toggle=\"yes\">Ruminococcus<\/jats:italic>\n                      species, including six previously unrecognized human symbionts. Structure-based clustering identifies several novel cohesin families that retain conserved folds despite extreme sequence divergence and define distinct, phylogenetically conserved cellulosome architectures. The analysis reveals\n                      <jats:italic toggle=\"yes\">R. callidus<\/jats:italic>\n                      and related human symbionts encode elaborate cellulosomes that are invisible to sequence-based annotation. Similarly,\n                      <jats:italic toggle=\"yes\">R. difficilis<\/jats:italic>\n                      , a human gut symbiont, has been found to possess genes for an atypical cohesin-based assembly enriched in amylases and related starch-binding proteins, which may enable this microbe to degrade resistant starches that evade digestion in the upper gastrointestinal tract. Together, these findings reveal that ruminococcal cellulosomes are far more prevalent and diverse than previously appreciated and demonstrate the power of structural proteomics to uncover deeply divergent functional systems in the gut microbiome.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Plant cell wall polysaccharides are a major dietary carbon source, yet their degradation relies on rare, highly specialized microbial enzyme assemblies known as cellulosomes, which have long been considered uncommon in the human gut. Using proteome-scale structure prediction combined with experimental validation, we show that cellulosomes are far more widespread and structurally diverse in human-associated\n                        <jats:italic toggle=\"yes\">Ruminococcus<\/jats:italic>\n                        species than previously appreciated. We identify multiple new cohesin families and reveal distinct cellulosome architectures likely adapted to degrade different dietary substrates. Together, these findings redefine the distribution and evolution of cellulosomes in gut microbes and demonstrate the power of structural proteomics to uncover deeply diverged biological systems.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.01295-26","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T13:06:17Z","timestamp":1784811977000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["AlphaFold-driven structural proteomics reveals extensive cellulosome machinery in human ruminococcal symbionts"],"prefix":"10.1128","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5342-3917","authenticated-orcid":false,"given":"Christine","family":"Minor","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/046rm7j60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of 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P.","family":"Gunsalus","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/046rm7j60","id-type":"ROR","asserted-by":"publisher"}],"name":"UCLA-DOE Institute of Genomics and Proteomics, University of California, Los Angeles","place":["Los Angeles, USA"]},{"id":[{"id":"https:\/\/ror.org\/046rm7j60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles","place":["Los Angeles, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Pellegrini","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/046rm7j60","id-type":"ROR","asserted-by":"publisher"}],"name":"UCLA-DOE Institute of Genomics and Proteomics, University of California, Los Angeles","place":["Los Angeles, USA"]},{"id":[{"id":"https:\/\/ror.org\/046rm7j60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular, Cell, and Developmental 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