{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:04:57Z","timestamp":1789556697637,"version":"build-2803163510"},"reference-count":68,"publisher":"AIP Publishing","issue":"11","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["MCB-1817948"],"award-info":[{"award-number":["MCB-1817948"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["MCB-2527485"],"award-info":[{"award-number":["MCB-2527485"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pubs.aip.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,9,21]]},"abstract":"<jats:p>Microtubule severing enzymes of the AAA+ family are essential regulators of cytoskeletal remodeling, extracting subunits from microtubules through Adenosine triphosphate (ATP)-driven conformational changes. Among them, katanin assembles into hexameric structures and binds the negatively charged carboxy-terminal tails (CTTs) of tubulin through its central pore. Experimental studies have shown that different CTT isotypes can act as either inhibitors or non-inhibitors of katanin-mediated severing, with increased CTT hydrophobicity associated with reduced inhibition. However, the molecular basis underlying this selective behavior remains poorly understood. Here, we employed molecular dynamics simulations and quantitative analysis combining principal component analysis, clustering, distance distribution analysis, and contact tracing to investigate how natural tubulin CTTs (beta5, beta4b, and beta3) and engineered CTTs (beta5-A+Y, beta5-cterm, beta5-midpoint, and poly-E) influence katanin structure and dynamics in spiral and ring conformations. We found that inhibitory CTTs form stronger interactions with the terminal protomers and increase flexibility in the inner protomers, resulting in coordinated motions associated with pore narrowing. In contrast, non-inhibitory CTTs preferentially interact with inner protomers, disrupting interprotomer coordination and weakening the collective interaction of the hexamer with the substrate. Analyses of the engineered constructs revealed that inhibitory behavior is governed primarily by the spatial distribution of acidic residues rather than the overall charge. In addition, using a fully modeled H. sapiens ring katanin structure, we identified species-specific responses of different CTT isotypes. These findings provide insight into how tubulin CTT sequence organization regulates substrate recognition and pore dynamics and, therefore, severing efficiency, leading to predictive design of CTTs with a desired action on katanin.<\/jats:p>","DOI":"10.1063\/5.0345522","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T10:31:42Z","timestamp":1789554702000},"update-policy":"https:\/\/doi.org\/10.1063\/aip-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Distinct tubulin C-terminal tails control the efficiency of a microtubule severing machine"],"prefix":"10.1063","volume":"165","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7007-821X","authenticated-orcid":false,"given":"Madhavie","family":"Ranpati Dewage","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Cincinnati 1 , Cincinnati, Ohio 45221,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6997-0507","authenticated-orcid":false,"given":"Shehani","family":"Kahawatte","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Cincinnati 1 , Cincinnati, Ohio 45221,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4838-3798","authenticated-orcid":false,"given":"Jennifer L.","family":"Ross","sequence":"additional","affiliation":[{"name":"Department of Physics, Syracuse University 2 , Syracuse, New York 13244,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6105-7287","authenticated-orcid":false,"given":"Ruxandra I.","family":"Dima","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Cincinnati 1 , Cincinnati, Ohio 45221,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"317","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"2026091606313645100_c1","article-title":"Microtubules","volume-title":"The Cell: A Molecular Approach","year":"2000","edition":"2"},{"key":"2026091606313645100_c2","doi-asserted-by":"publisher","first-page":"2924","DOI":"10.1091\/mbc.e16-05-0271","volume":"28","year":"2017","journal-title":"Mol. Biol. Cell"},{"key":"2026091606313645100_c3","doi-asserted-by":"publisher","first-page":"4057","DOI":"10.1083\/jcb.201612104","volume":"217","year":"2018","journal-title":"J.\u00a0Cell Biol."},{"key":"2026091606313645100_c4","doi-asserted-by":"publisher","first-page":"433003","DOI":"10.1088\/1361-648x\/aa8670","volume":"29","year":"2017","journal-title":"J.\u00a0Phys.: Condens. Matter"},{"key":"2026091606313645100_c5","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1016\/j.tcb.2019.07.004","volume":"29","year":"2019","journal-title":"Trends Cell Biol."},{"key":"2026091606313645100_c6","doi-asserted-by":"publisher","first-page":"1623181","DOI":"10.1155\/2022\/1623181","volume":"2022","journal-title":"Oxid. Med. Cell. Longevity"},{"key":"2026091606313645100_c7","doi-asserted-by":"publisher","first-page":"3437","DOI":"10.1016\/j.bpj.2021.05.027","volume":"120","year":"2021","journal-title":"Biophys. J."},{"key":"2026091606313645100_c8","doi-asserted-by":"publisher","first-page":"125102","DOI":"10.1063\/5.0139273","volume":"158","year":"2023","journal-title":"J.\u00a0Chem. Phys."},{"key":"2026091606313645100_c9","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.1091\/mbc.9.7.1847","volume":"9","year":"1998","journal-title":"Mol. Biol. Cell"},{"key":"2026091606313645100_c10","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1021\/acs.biochem.4c00693","volume":"64","year":"2025","journal-title":"Biochemistry"},{"key":"2026091606313645100_c11","doi-asserted-by":"publisher","first-page":"5533","DOI":"10.1073\/pnas.1818824116","volume":"116","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2026091606313645100_c12","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1083\/jcb.145.2.305","volume":"145","year":"1999","journal-title":"J.\u00a0Cell Biol."},{"key":"2026091606313645100_c13","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1242\/dev.097774","volume":"141","year":"2014","journal-title":"Development"},{"key":"2026091606313645100_c14","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.devcel.2019.10.010","volume":"52","year":"2020","journal-title":"Dev. Cell"},{"key":"2026091606313645100_c15","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1038\/mp.2017.54","volume":"23","year":"2018","journal-title":"Mol. Psychiatry"},{"key":"2026091606313645100_c16","doi-asserted-by":"publisher","first-page":"e1002697","DOI":"10.1371\/journal.pgen.1002697","volume":"8","year":"2012","journal-title":"PLoS Genet."},{"key":"2026091606313645100_c17","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1038\/nsmb.3448","volume":"24","year":"2017","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2026091606313645100_c18","doi-asserted-by":"publisher","first-page":"10590","DOI":"10.1074\/jbc.ra117.001215","volume":"293","year":"2018","journal-title":"J.\u00a0Biol. Chem."},{"key":"2026091606313645100_c19","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1002\/cm.21606","volume":"77","year":"2020","journal-title":"Cytoskeleton"},{"key":"2026091606313645100_c20","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","volume":"14","year":"1996","journal-title":"J.\u00a0Mol. Graphics"},{"key":"2026091606313645100_c21","doi-asserted-by":"publisher","first-page":"2546","DOI":"10.1016\/j.bpj.2015.11.011","volume":"109","year":"2015","journal-title":"Biophys. J."},{"key":"2026091606313645100_c22","doi-asserted-by":"publisher","first-page":"4888","DOI":"10.1021\/acs.jpcb.9b03059","volume":"123","year":"2019","journal-title":"J.\u00a0Phys. Chem. B"},{"key":"2026091606313645100_c23","doi-asserted-by":"publisher","first-page":"1849","DOI":"10.3390\/nano12111849","volume":"12","year":"2022","journal-title":"Nanomaterials"},{"key":"2026091606313645100_c24","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/s41594-019-0257-3","volume":"26","year":"2019","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2026091606313645100_c25","doi-asserted-by":"publisher","first-page":"e201800059","DOI":"10.26508\/lsa.201800059","volume":"1","year":"2018","journal-title":"Life Sci. Alliance"},{"key":"2026091606313645100_c26","doi-asserted-by":"publisher","first-page":"jcs259539","DOI":"10.1242\/jcs.259539","volume":"135","year":"2022","journal-title":"J.\u00a0Cell Sci."},{"key":"2026091606313645100_c27","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1038\/s41580-020-0214-3","volume":"21","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2026091606313645100_c28","doi-asserted-by":"publisher","first-page":"860065","DOI":"10.3389\/fcell.2022.860065","volume":"10","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"2026091606313645100_c29","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1038\/s42003-023-05306-y","volume":"6","year":"2023","journal-title":"Commun. Biol."},{"key":"2026091606313645100_c30","doi-asserted-by":"publisher","first-page":"851542","DOI":"10.3389\/fcell.2022.851542","volume":"10","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"2026091606313645100_c31","doi-asserted-by":"publisher","first-page":"1554","DOI":"10.1016\/j.celrep.2012.11.017","volume":"2","year":"2012","journal-title":"Cell Rep."},{"key":"2026091606313645100_c32","doi-asserted-by":"publisher","first-page":"dev201819","DOI":"10.1242\/dev.201819","volume":"151","year":"2024","journal-title":"Development"},{"key":"2026091606313645100_c33","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1038\/s42003-024-06867-2","volume":"7","year":"2024","journal-title":"Commun. Biol."},{"key":"2026091606313645100_c34","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1016\/j.celrep.2019.01.020","volume":"26","year":"2019","journal-title":"Cell Rep."},{"key":"2026091606313645100_c35","doi-asserted-by":"publisher","first-page":"11762","DOI":"10.1074\/jbc.m114.614768","volume":"290","year":"2015","journal-title":"J.\u00a0Biol. Chem."},{"key":"2026091606313645100_c36","doi-asserted-by":"publisher","first-page":"jcs261070","DOI":"10.1242\/jcs.261070","volume":"136","year":"2023","journal-title":"J.\u00a0Cell Sci."},{"key":"2026091606313645100_c37","doi-asserted-by":"publisher","first-page":"2497","DOI":"10.1016\/j.devcel.2022.10.003","volume":"57","year":"2022","journal-title":"Dev. Cell"},{"key":"2026091606313645100_c38","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1083\/jcb.200704021","volume":"178","year":"2007","journal-title":"J.\u00a0Cell Biol."},{"key":"2026091606313645100_c39","doi-asserted-by":"publisher","first-page":"620","DOI":"10.3390\/biom13040620","volume":"13","year":"2023","journal-title":"Biomolecules"},{"key":"2026091606313645100_c40","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1091\/mbc.e03-06-0418","volume":"15","year":"2004","journal-title":"Mol. Biol. Cell"},{"key":"2026091606313645100_c41","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1093\/nar\/28.1.235","volume":"28","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"2026091606313645100_c42","article-title":"The PyMOL molecular graphics system","author":"Schr\u00f6dinger, LLC","year":"2015"},{"key":"2026091606313645100_c43","doi-asserted-by":"publisher","first-page":"btac793","DOI":"10.1093\/bioinformatics\/btac793","volume":"39","year":"2022","journal-title":"Bioinformatics"},{"key":"2026091606313645100_c44","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1002\/jcc.20291","volume":"26","year":"2005","journal-title":"J.\u00a0Comput. Chem."},{"key":"2026091606313645100_c45","doi-asserted-by":"publisher","first-page":"W310","DOI":"10.1093\/nar\/gkl206","volume":"34","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"2026091606313645100_c46","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.1093\/bioinformatics\/btu097","volume":"30","year":"2014","journal-title":"Bioinformatics"},{"key":"2026091606313645100_c47","doi-asserted-by":"publisher","first-page":"3219","DOI":"10.1038\/s41596-024-01011-0","volume":"19","year":"2024","journal-title":"Nat. Protoc."},{"key":"2026091606313645100_c48","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","volume":"630","year":"2024","journal-title":"Nature"},{"key":"2026091606313645100_c49","doi-asserted-by":"publisher","first-page":"169949","DOI":"10.1016\/j.jmb.2026.169949","volume":"438","year":"2026","journal-title":"J.\u00a0Mol. Biol."},{"key":"2026091606313645100_c50","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1006\/jmbi.1993.1626","volume":"234","year":"1993","journal-title":"J.\u00a0Mol. Biol."},{"key":"2026091606313645100_c51","doi-asserted-by":"publisher","first-page":"e4792","DOI":"10.1002\/pro.4792","volume":"32","year":"2023","journal-title":"Protein Sci."},{"key":"2026091606313645100_c52","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1007\/s00249-011-0700-9","volume":"40","year":"2011","journal-title":"Eur. Biophys. J."},{"key":"2026091606313645100_c53","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1103\/physrev.159.98","volume":"159","year":"1967","journal-title":"Phys. Rev."},{"key":"2026091606313645100_c54","doi-asserted-by":"publisher","first-page":"014101","DOI":"10.1063\/1.2408420","volume":"126","year":"2007","journal-title":"J.\u00a0Chem. Phys."},{"key":"2026091606313645100_c55","doi-asserted-by":"publisher","first-page":"7182","DOI":"10.1063\/1.328693","volume":"52","year":"1981","journal-title":"J.\u00a0Appl. Phys."},{"key":"2026091606313645100_c56","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1002\/(SICI)1096-987X(199709)18:12&lt;1463::AID-JCC4&gt;3.0.CO;2-H","volume":"18","year":"1997","journal-title":"J.\u00a0Comput. Chem."},{"key":"2026091606313645100_c57","doi-asserted-by":"publisher","first-page":"10089","DOI":"10.1063\/1.464397","volume":"98","year":"1993","journal-title":"J.\u00a0Chem. Phys."},{"key":"2026091606313645100_c58","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1002\/(sici)1097-0134(19990215)34:3&lt;269::aid-prot1&gt;3.0.co;2-3","volume":"34","year":"1999","journal-title":"Proteins: Struct., Funct., Genet."},{"key":"2026091606313645100_c59","doi-asserted-by":"publisher","first-page":"102238","DOI":"10.1016\/j.jbc.2022.102238","volume":"298","year":"2022","journal-title":"J.\u00a0Biol. Chem."},{"key":"2026091606313645100_c60","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1021\/acs.jcim.3c01511","volume":"64","year":"2024","journal-title":"J.\u00a0Chem. Inf. Model."},{"key":"2026091606313645100_c61","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1002\/(sici)1521-3773(19990115)38:1\/2&lt;236::aid-anie236&gt;3.0.co;2-m","volume":"38","year":"1999","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026091606313645100_c62","doi-asserted-by":"publisher","first-page":"2733","DOI":"10.1103\/physrevlett.80.2733","volume":"80","year":"1998","journal-title":"Phys. Rev. Lett."},{"key":"2026091606313645100_c63","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1002\/(sici)1097-0134(19990515)35:3&lt;283::aid-prot2&gt;3.0.co;2-r","volume":"35","year":"1999","journal-title":"Proteins: Struct., Funct., Genet."},{"key":"2026091606313645100_c64","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.jmgm.2011.08.004","volume":"31","year":"2011","journal-title":"J.\u00a0Mol. Graphics Modell."},{"key":"2026091606313645100_c65","doi-asserted-by":"publisher","first-page":"150901","DOI":"10.1063\/1.5091842","volume":"150","year":"2019","journal-title":"J.\u00a0Chem. Phys."},{"key":"2026091606313645100_c66","doi-asserted-by":"publisher","first-page":"46","DOI":"10.3389\/fmolb.2019.00046","volume":"6","year":"2019","journal-title":"Front. Mol. Biosci."},{"key":"2026091606313645100_c67","first-page":"98","year":"2016"},{"key":"2026091606313645100_c68","doi-asserted-by":"publisher","first-page":"e0226702","DOI":"10.1371\/journal.pone.0226702","volume":"15","year":"2020","journal-title":"PLoS One"}],"container-title":["The Journal of Chemical Physics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.aip.org\/aip\/jcp\/article-pdf\/doi\/10.1063\/5.0345522\/21141042\/115102_1_5.0345522.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.aip.org\/aip\/jcp\/article-pdf\/doi\/10.1063\/5.0345522\/21141042\/115102_1_5.0345522.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T10:31:44Z","timestamp":1789554704000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.aip.org\/jcp\/article\/165\/11\/115102\/3404607\/Distinct-tubulin-C-terminal-tails-control-the"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":68,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2026,9,21]]}},"URL":"https:\/\/doi.org\/10.1063\/5.0345522","relation":{},"ISSN":["0021-9606","1089-7690"],"issn-type":[{"value":"0021-9606","type":"print"},{"value":"1089-7690","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,9,21]]},"published":{"date-parts":[[2026,9,16]]},"article-number":"115102"}}