Conformational plasticity of the ULK3 kinase domain

Conformational plasticity of the ULK3 kinase domain

The human protein kinase ULK3 regulates the timing of membrane abscission, thus being involved in exosome budding and cytokinesis. Herein, we present the first high-resolution structures of the ULK3 kinase domain. Its unique features are explored against the background of other ULK kinases. An inhib...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Biochemical journal 2021-07, Vol.478 (14), p.2811-2823
Hauptverfasser: Mathea, Sebastian, Salah, Eidarus, Tallant, Cynthia, Chatterjee, Deep, Berger, Benedict-Tilman, Konietzny, Rebecca, Müller, Susanne, Kessler, Benedikt M., Knapp, Stefan
Format: Artikel
Sprache:eng
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 2823
container_issue 14
container_start_page 2811
container_title Biochemical journal
container_volume 478
creator Mathea, Sebastian
Salah, Eidarus
Tallant, Cynthia
Chatterjee, Deep
Berger, Benedict-Tilman
Konietzny, Rebecca
Müller, Susanne
Kessler, Benedikt M.
Knapp, Stefan
description The human protein kinase ULK3 regulates the timing of membrane abscission, thus being involved in exosome budding and cytokinesis. Herein, we present the first high-resolution structures of the ULK3 kinase domain. Its unique features are explored against the background of other ULK kinases. An inhibitor fingerprint indicates that ULK3 is highly druggable and capable of adopting a wide range of conformations. In accordance with this, we describe a conformational switch between the active and an inactive ULK3 conformation, controlled by the properties of the attached small-molecule binder. Finally, we discuss a potential substrate-recognition mechanism of the full-length ULK3 protein.
doi_str_mv 10.1042/BCJ20210257
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2546976063</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2546976063</sourcerecordid><originalsourceid>FETCH-LOGICAL-c303t-44f16aca4de19f147ce73a0ce35e0835423aaadaa03307e47c82e9f4f37dccbf3</originalsourceid><addsrcrecordid>eNpNkD1PxDAQRC0EEuGg4g-kREKBtdeJcyVEfEei4epocdbCkMQhzhX37wk6Cqop3mg0ekKcS7iSoNX1bfWsQElQuTkQidQGstKo8lAkoAqdFQs7FicxfgJIDRoSgVUYXJh6mn0YqEvHjuLsrZ93aXDp_MHppn7B9MsPFDltQ09-OBVHjrrIZ3-5Epv7u7fqMatfH56qmzqzCDhnWjtZkCXdsly75YxlgwSWMWcoMdcKiaglAkQwvPBS8dpph6a19t3hSlzsd8cpfG85zk3vo-Wuo4HDNjYq18XaFFDgUr3cV-0UYpzYNePke5p2jYTmV03zTw3-ACVtVUE</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2546976063</pqid></control><display><type>article</type><title>Conformational plasticity of the ULK3 kinase domain</title><source>Portland Press Electronic Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Mathea, Sebastian ; Salah, Eidarus ; Tallant, Cynthia ; Chatterjee, Deep ; Berger, Benedict-Tilman ; Konietzny, Rebecca ; Müller, Susanne ; Kessler, Benedikt M. ; Knapp, Stefan</creator><creatorcontrib>Mathea, Sebastian ; Salah, Eidarus ; Tallant, Cynthia ; Chatterjee, Deep ; Berger, Benedict-Tilman ; Konietzny, Rebecca ; Müller, Susanne ; Kessler, Benedikt M. ; Knapp, Stefan</creatorcontrib><description>The human protein kinase ULK3 regulates the timing of membrane abscission, thus being involved in exosome budding and cytokinesis. Herein, we present the first high-resolution structures of the ULK3 kinase domain. Its unique features are explored against the background of other ULK kinases. An inhibitor fingerprint indicates that ULK3 is highly druggable and capable of adopting a wide range of conformations. In accordance with this, we describe a conformational switch between the active and an inactive ULK3 conformation, controlled by the properties of the attached small-molecule binder. Finally, we discuss a potential substrate-recognition mechanism of the full-length ULK3 protein.</description><identifier>ISSN: 0264-6021</identifier><identifier>EISSN: 1470-8728</identifier><identifier>DOI: 10.1042/BCJ20210257</identifier><language>eng</language><ispartof>Biochemical journal, 2021-07, Vol.478 (14), p.2811-2823</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c303t-44f16aca4de19f147ce73a0ce35e0835423aaadaa03307e47c82e9f4f37dccbf3</citedby><cites>FETCH-LOGICAL-c303t-44f16aca4de19f147ce73a0ce35e0835423aaadaa03307e47c82e9f4f37dccbf3</cites><orcidid>0000-0001-8500-4569</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,3255,27907,27908</link.rule.ids></links><search><creatorcontrib>Mathea, Sebastian</creatorcontrib><creatorcontrib>Salah, Eidarus</creatorcontrib><creatorcontrib>Tallant, Cynthia</creatorcontrib><creatorcontrib>Chatterjee, Deep</creatorcontrib><creatorcontrib>Berger, Benedict-Tilman</creatorcontrib><creatorcontrib>Konietzny, Rebecca</creatorcontrib><creatorcontrib>Müller, Susanne</creatorcontrib><creatorcontrib>Kessler, Benedikt M.</creatorcontrib><creatorcontrib>Knapp, Stefan</creatorcontrib><title>Conformational plasticity of the ULK3 kinase domain</title><title>Biochemical journal</title><description>The human protein kinase ULK3 regulates the timing of membrane abscission, thus being involved in exosome budding and cytokinesis. Herein, we present the first high-resolution structures of the ULK3 kinase domain. Its unique features are explored against the background of other ULK kinases. An inhibitor fingerprint indicates that ULK3 is highly druggable and capable of adopting a wide range of conformations. In accordance with this, we describe a conformational switch between the active and an inactive ULK3 conformation, controlled by the properties of the attached small-molecule binder. Finally, we discuss a potential substrate-recognition mechanism of the full-length ULK3 protein.</description><issn>0264-6021</issn><issn>1470-8728</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNpNkD1PxDAQRC0EEuGg4g-kREKBtdeJcyVEfEei4epocdbCkMQhzhX37wk6Cqop3mg0ekKcS7iSoNX1bfWsQElQuTkQidQGstKo8lAkoAqdFQs7FicxfgJIDRoSgVUYXJh6mn0YqEvHjuLsrZ93aXDp_MHppn7B9MsPFDltQ09-OBVHjrrIZ3-5Epv7u7fqMatfH56qmzqzCDhnWjtZkCXdsly75YxlgwSWMWcoMdcKiaglAkQwvPBS8dpph6a19t3hSlzsd8cpfG85zk3vo-Wuo4HDNjYq18XaFFDgUr3cV-0UYpzYNePke5p2jYTmV03zTw3-ACVtVUE</recordid><startdate>20210730</startdate><enddate>20210730</enddate><creator>Mathea, Sebastian</creator><creator>Salah, Eidarus</creator><creator>Tallant, Cynthia</creator><creator>Chatterjee, Deep</creator><creator>Berger, Benedict-Tilman</creator><creator>Konietzny, Rebecca</creator><creator>Müller, Susanne</creator><creator>Kessler, Benedikt M.</creator><creator>Knapp, Stefan</creator><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-8500-4569</orcidid></search><sort><creationdate>20210730</creationdate><title>Conformational plasticity of the ULK3 kinase domain</title><author>Mathea, Sebastian ; Salah, Eidarus ; Tallant, Cynthia ; Chatterjee, Deep ; Berger, Benedict-Tilman ; Konietzny, Rebecca ; Müller, Susanne ; Kessler, Benedikt M. ; Knapp, Stefan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c303t-44f16aca4de19f147ce73a0ce35e0835423aaadaa03307e47c82e9f4f37dccbf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mathea, Sebastian</creatorcontrib><creatorcontrib>Salah, Eidarus</creatorcontrib><creatorcontrib>Tallant, Cynthia</creatorcontrib><creatorcontrib>Chatterjee, Deep</creatorcontrib><creatorcontrib>Berger, Benedict-Tilman</creatorcontrib><creatorcontrib>Konietzny, Rebecca</creatorcontrib><creatorcontrib>Müller, Susanne</creatorcontrib><creatorcontrib>Kessler, Benedikt M.</creatorcontrib><creatorcontrib>Knapp, Stefan</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mathea, Sebastian</au><au>Salah, Eidarus</au><au>Tallant, Cynthia</au><au>Chatterjee, Deep</au><au>Berger, Benedict-Tilman</au><au>Konietzny, Rebecca</au><au>Müller, Susanne</au><au>Kessler, Benedikt M.</au><au>Knapp, Stefan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Conformational plasticity of the ULK3 kinase domain</atitle><jtitle>Biochemical journal</jtitle><date>2021-07-30</date><risdate>2021</risdate><volume>478</volume><issue>14</issue><spage>2811</spage><epage>2823</epage><pages>2811-2823</pages><issn>0264-6021</issn><eissn>1470-8728</eissn><abstract>The human protein kinase ULK3 regulates the timing of membrane abscission, thus being involved in exosome budding and cytokinesis. Herein, we present the first high-resolution structures of the ULK3 kinase domain. Its unique features are explored against the background of other ULK kinases. An inhibitor fingerprint indicates that ULK3 is highly druggable and capable of adopting a wide range of conformations. In accordance with this, we describe a conformational switch between the active and an inactive ULK3 conformation, controlled by the properties of the attached small-molecule binder. Finally, we discuss a potential substrate-recognition mechanism of the full-length ULK3 protein.</abstract><doi>10.1042/BCJ20210257</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-8500-4569</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0264-6021
ispartof Biochemical journal, 2021-07, Vol.478 (14), p.2811-2823
issn 0264-6021
1470-8728
language eng
recordid cdi_proquest_miscellaneous_2546976063
source Portland Press Electronic Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central
title Conformational plasticity of the ULK3 kinase domain
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-17T00%3A36%3A36IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Conformational%20plasticity%20of%20the%20ULK3%20kinase%20domain&rft.jtitle=Biochemical%20journal&rft.au=Mathea,%20Sebastian&rft.date=2021-07-30&rft.volume=478&rft.issue=14&rft.spage=2811&rft.epage=2823&rft.pages=2811-2823&rft.issn=0264-6021&rft.eissn=1470-8728&rft_id=info:doi/10.1042/BCJ20210257&rft_dat=%3Cproquest_cross%3E2546976063%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2546976063&rft_id=info:pmid/&rfr_iscdi=true