https://m2.mtmt.hu/ hun 2026-09-21 13:38 JournalArticle 32573094 VALIDATED true Department of Biochemistry, Semmelweis University, Budapest, Hungary HCEMM-SE Molecular Channelopathies Research Group, Budapest, Hungary MTA-SE Ion Channel Research Group, Semmelweis University, Budapest, Hungary Cited By :9 Export Date: 24 July 2024 Correspondence Address: Csanády, L.; Department of Biochemistry, Hungary; email: csanady.laszlo@med.semmelweis-univ.hu 0 false 2026-06-17T11:51:52.542+0000 2026-05-28T06:49:16.551+0000 2022-01-05T09:27:32.289+0000 true 10080205 Szalóky-Siki Ágnes /api/admin/10080205 Admin true 2026-05-28T06:49:17.710+0000 2026-05-28T06:49:17.710+0000 2023-11-29T14:08:45.896+0000 true 10062250 Molnár-Taga Márta /api/admin/10062250 Admin true 10062250 Admin 10003134 /api/admin/10003134 Wolf György true 10003134 true Admin 10067876 /api/admin/10067876 Ladányi Gusztáv true true 2024-10-17T16:09:40.962+0000 true false true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle true 10000059 Article true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle /api/subtype/10000059 Szakcikk SubType 101 true 10000059 true 1 /api/category/1 Category true 1 Simon, Marton A. Molecular pathology of the R117H cystic fibrosis mutation is explained by loss of a hydrogen bond true true /api/journal/10031024 REVIEWED true false 10031024 false 10031024 true 2050-084X Journal FOREIGN 10 e74693 e74693 19 2021 The phosphorylation-activated anion channel cystic fibrosis transmembrane conductance regulator (CFTR) is gated by an ATP hydrolysis cycle at its two cytosolic nucleotide-binding domains, and is essential for epithelial salt-water transport. A large number of CFTR mutations cause cystic fibrosis. Since recent breakthrough in targeted pharmacotherapy, CFTR mutants with impaired gating are candidates for stimulation by potentiator drugs. Thus, understanding the molecular pathology of individual mutations has become important. The relatively common R117H mutation affects an extracellular loop, but nevertheless causes a strong gating defect. Here, we identify a hydrogen bond between the side chain of arginine 117 and the backbone carbonyl group of glutamate 1124 in the cryo-electronmicroscopic structure of phosphorylated, ATP-bound CFTR. We address the functional relevance of that interaction for CFTR gating using macroscopic and microscopic inside-out patch-clamp recordings. Employing thermodynamic double-mutant cycles, we systematically track gating-state-dependent changes in the strength of the R117-E1124 interaction. We find that the H-bond is formed only in the open state, but neither in the short-lived 'flickery' nor in the long-lived 'interburst' closed state. Loss of this H-bond explains the strong gating phenotype of the R117H mutant, including robustly shortened burst durations and strongly reduced intraburst open probability. The findings may help targeted potentiator design. Funding 2012817 /api/funding/2012817 false true Funding 2012818 /api/funding/2012818 false true Funding 2012819 /api/funding/2012819 false true Funding 2012820 /api/funding/2012820 false true Funding 2012821 /api/funding/2012821 false true true true 2022 true true true false true false GOLD 2026-06-17 true https://doi.org/10.7554/eLife.74693 16 0 15 11 4 15 15 15 13 16 15 12 11 12 4 0 16 12 15 11 0 10 10 Folyóiratcikk Journal Article 24 13 Könyvrészlet Chapter in Book 25 2 Könyv Book 23 0 Egyéb konferenciaközlemény Conference paper 31 0 Egyéb konferenciakötet Conference proceedings 32 0 Oltalmi formák Protection forms 26 0 Disszertáció Thesis 28 0 Egyéb Miscellaneous 29 1 Alkotás Achievement 22 0 Kutatási adat Research data 33 0 Folyóiratcikk Journal Article 24 0 0 0 Könyvrészlet Chapter in Book 25 0 0 0 Könyv Book 23 0 0 0 Egyéb konferenciaközlemény Conference paper 31 0 0 0 Egyéb konferenciakötet Conference proceedings 32 0 0 0 Oltalmi formák Protection forms 26 0 0 0 Disszertáció Thesis 28 0 0 0 Egyéb Miscellaneous 29 0 0 0 Alkotás Achievement 22 0 0 0 Kutatási adat Research data 33 0 0 0 2022 0 3 3 3 3 2023 0 6 4 6 4 2024 0 5 3 5 3 2025 0 1 1 1 1 2026 0 1 1 1 1 D1 false false false false 2022-01-04T09:29:54.917+0000 Biokémiai Tanszék (SE / AOK / I / BMBI); Biokémiai és Molekuláris Biológiai Intézet (SE / AOK / I); HCEMM-SE Molekuláris Csatornabetegségek Kutatóc... (SE / AOK / I / BMBI / BT); MTA-SE Lendület Ioncsatorna Kutatócsoport (SE / AOK / I / BMBI / BT) 2 18 4 2 0 true 10003134 10067876 Language 10002 /api/language/10002 Angol English true 2 true PersonAuthorship 99886579 /api/authorship/99886579 1 0.5 true false false Author 10066737 /api/author/10066737 Simon Márton true true Simon Marton A. true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 99886580 /api/authorship/99886580 2 0.5 false true true Author 10015499 /api/author/10015499 Csanády László true 10015499 true Csanady Laszlo true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PublicationIdentifier 21342230 /api/publicationidentifier/21342230 PlainSource 6 /api/publicationsource/6 PublicationSourceType 10001 /api/publicationsourcetype/10001 true true true DOI DOI https://doi.org/@@@ true true 6 true GOLD true IDENTICAL 10.7554/eLife.74693 https://doi.org/10.7554/eLife.74693 false true PublicationIdentifier 20364223 /api/publicationidentifier/20364223 PlainSource 1 /api/publicationsource/1 PublicationSourceType 10003 /api/publicationsourcetype/10003 false true true WoS WoS https://www.webofscience.com/wos/woscc/full-record/@@@ true true 1 true IDENTICAL 000730939900001 https://www.webofscience.com/wos/woscc/full-record/000730939900001 false true PublicationIdentifier 20394464 /api/publicationidentifier/20394464 PlainSource 3 /api/publicationsource/3 PublicationSourceType 10003 /api/publicationsourcetype/10003 false true true Scopus Scopus http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-@@@ true true 3 true IDENTICAL 85122026620 http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85122026620 true true PublicationIdentifier 20364224 /api/publicationidentifier/20364224 PlainSource 17 /api/publicationsource/17 PublicationSourceType 10003 /api/publicationsourcetype/10003 false true true PubMed PubMed http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=@@@&dopt=Abstract true true 17 true IDENTICAL 34870594 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=34870594&dopt=Abstract false true PublicationIdentifier 31874387 /api/publicationidentifier/31874387 PlainSource 40 /api/publicationsource/40 PublicationSourceType 10006 /api/publicationsourcetype/10006 true true true Egyéb URL Other URL @@@ true true 40 true NONE IDENTICAL https://www.scopus.com/pages/publications/85122026620?origin=resultslist https://www.scopus.com/pages/publications/85122026620?origin=resultslist false true Keyword 81 /api/keyword/81 true 81 true Keyword 115 /api/keyword/115 true 115 true Keyword 477 /api/keyword/477 true 477 true Keyword 570 /api/keyword/570 true 570 true Keyword 1201 /api/keyword/1201 true 1201 true Keyword 10710 /api/keyword/10710 true 10710 true Keyword 1022667 /api/keyword/1022667 true 1022667 true Keyword 1548927 /api/keyword/1548927 true true Keyword 1634291 /api/keyword/1634291 true true Keyword 1755459 /api/keyword/1755459 true true Keyword 2023313 /api/keyword/2023313 true true Keyword 2558764 /api/keyword/2558764 true true Keyword 2558765 /api/keyword/2558765 true true SjrRating 11195761 /api/sjrrating/11195761 11 0.1 journal RatingType 10002 /api/ratingtype/10002 sjr true true ClassificationExternal 1301 /api/classificationexternal/1301 true 1301 true D1 DIRECT true true /api/publication/32573094 <div class="JournalArticle Publication long-list"> <div class="authors"> <img title="Forrásközlemény" style="float: left" src="/frontend/resources/grid/publication-core-icon.png"> <img title="Idézőközlemény" style="float: left" src="/frontend/resources/grid/publication-citation-icon.png"> <div class="autype autype0"> <span class="author-name" mtid="10066737"><a href="/gui2/?type=authors&mode=browse&sel=10066737" target="_blank">Simon Marton A. (<span class="authorship-author-name">Simon Márton</span> <span class="authorAux-mtmt"> Biokémia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Biokémiai és Molekuláris Biológiai Intézet; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/<span title="Biokémiai és Molekuláris Biológiai Intézet">BMBI</span>/Biokémiai Tanszék; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/<span title="Biokémiai és Molekuláris Biológiai Intézet">BMBI</span>/<span title="Biokémiai Tanszék">BT</span>/HCEMM-SE Molekuláris Csatornabetegségek Kutatócsoport</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10015499"><a href="/gui2/?type=authors&mode=browse&sel=10015499" target="_blank">Csanady Laszlo ✉ (<span class="authorship-author-name">Csanády László</span> <span class="authorAux-mtmt"> Biokémia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/<span title="Biokémiai és Molekuláris Biológiai Intézet">BMBI</span>/<span title="Biokémiai Tanszék">BT</span>/MTA-SE Lendület Ioncsatorna Kutatócsoport; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Biokémiai és Molekuláris Biológiai Intézet; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/<span title="Biokémiai és Molekuláris Biológiai Intézet">BMBI</span>/Biokémiai Tanszék; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/<span title="Biokémiai és Molekuláris Biológiai Intézet">BMBI</span>/<span title="Biokémiai Tanszék">BT</span>/HCEMM-SE Molekuláris Csatornabetegségek Kutatócsoport</span> </div> </div> <div class="title"><a href="/gui2/?mode=browse&params=publication;32573094" target="_blank">Molecular pathology of the R117H cystic fibrosis mutation is explained by loss of a hydrogen bond</a></div> <div> <span class="journal-title">ELIFE</span> <span class="journal-issn">( <a target="_blank" href="https://portal.issn.org/resource/ISSN/2050-084X">2050-084X</a>)</span>: <span class="journal-volume">10</span> <span class="page"> Paper e74693. 19 p. </span> <span class="year">(2021)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Nyelv: Angol | </span> <span class="identifiers"> <span class="id identifier oa_GOLD" title=" Gold "> <a style="color:blue" title="10.7554/eLife.74693" target="_blank" href="https://doi.org/10.7554/eLife.74693"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000730939900001" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000730939900001"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85122026620" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85122026620"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="34870594" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=34870594&dopt=Abstract"> PubMed </a> </span> <span class="id identifier oa_NONE" title=" Nincs "> <a style="color:blue" title="https://www.scopus.com/pages/publications/85122026620?origin=resultslist" target="_blank" href="https://www.scopus.com/pages/publications/85122026620?origin=resultslist"> Egyéb URL </a> </span> </span> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Folyóirat szakterülete: Scopus - Biochemistry, Genetics and Molecular Biology (miscellaneous)&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Immunology and Microbiology (miscellaneous)&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Medicine (miscellaneous)&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Neuroscience (miscellaneous)&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> </div></OnlyViewableByAuthor> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 16</span> | Független: 12 | Függő: 4 | Nem jelölt: 0 | WoS jelölt: 15 | Scopus jelölt:&nbsp;13 | WoS/Scopus jelölt:&nbsp;16 | DOI jelölt:&nbsp;15 </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;32573094&sort=publishedYear,desc&sort=title"> Idézett közlemények száma: 10 </a> </div> <div class="mtid"><span class="long-pub-mtid">Közlemény: 32573094</span> | <span class="status-data status-VALIDATED"> Egyeztetett </span> Forrás Idéző | <span class="type-subtype">Folyóiratcikk ( Szakcikk ) </span> | <span class="pub-category">Tudományos</span> | <span class="publication-sourceOfData">WOS TAGGED</span> </div> <div class="funder"> HCEMM(739593) Támogató: Horizon 2020, (LP2017-14/2017), (Lendület) Támogató: MTA, (CSANAD21G0), (ÚNKP-20–3-I-SE-34) </div> <div class="notDuplums"><a target="_blank" href="/api/publication/32573094/notduplums">1 Nem duplumnak jelölés</a> </div> <div class="lastModified">Utolsó módosítás: 2026.05.28. 08:49 Molnár-Taga Márta (SE 4-es admin) </div> <div class="lockedBy">Központi kezelésű 2024.10.17. 18:09 Wolf György (MTMT Központi admin) Ladányi Gusztáv (MTMT API user, admin) </div> <pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Megjegyzés</u>: Department of Biochemistry, Semmelweis University, Budapest, Hungary HCEMM-SE Molecular Channelopathies Research Group, Budapest, Hungary MTA-SE Ion Channel Research Group, Semmelweis University, Budapest, Hungary Cited By :9 Export Date: 24 July 2024 Correspondence Address: C...</pre> </div></div>