Počet záznamů: 1
A structural model of the iRhom-ADAM17 sheddase complex reveals functional insights into its trafficking and activity
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SYSNO ASEP 0572295 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název A structural model of the iRhom-ADAM17 sheddase complex reveals functional insights into its trafficking and activity Tvůrce(i) Kahveci-Tuerkoez, S. (DE)
Blaesius, K. (DE)
Wozniak, J. (DE)
Rinkens, C. (DE)
Seifert, A. (DE)
Kašpárek, Petr (UMG-J)
Ohm, H. (DE)
Oltzen, S. (DE)
Nieszporek, M. (DE)
Schwarz, N. (DE)
Babendreyer, A. (DE)
Preisinger, C. (DE)
Sedláček, Radislav (UMG-J) RID
Ludwig, A. (DE)
Duesterhoeft, S. (DE)Celkový počet autorů 15 Číslo článku 135 Zdroj.dok. Cellular and Molecular Life Sciences - ISSN 1420-682X
Roč. 80, č. 5 (2023)Poč.str. 21 s. Jazyk dok. eng - angličtina Země vyd. CH - Švýcarsko Klíč. slova iRhom ; adam17 ; Ectodomain shedding ; TNF signalling ; EGFR ligand release iRhom-ADAM17 complex structure ; iRhom homology domain Obor OECD Biochemistry and molecular biology CEP LM2018126 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access Institucionální podpora UMG-J - RVO:68378050 UT WOS 000978465900001 EID SCOPUS 85156136892 DOI 10.1007/s00018-023-04783-y Anotace Several membrane-anchored signal mediators such as cytokines (e.g. TNF alpha) and growth factors are proteolytically shed from the cell surface by the metalloproteinase ADAM17, which, thus, has an essential role in inflammatory and developmental processes. The membrane proteins iRhom1 and iRhom2 are instrumental for the transport of ADAM17 to the cell surface and its regulation. However, the structure-function determinants of the iRhom-ADAM17 complex are poorly understood. We used AI-based modelling to gain insights into the structure-function relationship of this complex. We identified different regions in the iRhom homology domain (IRHD) that are differentially responsible for iRhom functions. We have supported the validity of the predicted structure-function determinants with several in vitro, ex vivo and in vivo approaches and demonstrated the regulatory role of the IRHD for iRhom-ADAM17 complex cohesion and forward trafficking. Overall, we provide mechanistic insights into the iRhom-ADAM17-mediated shedding event, which is at the centre of several important cytokine and growth factor pathways. Pracoviště Ústav molekulární genetiky Kontakt Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Rok sběru 2024 Elektronická adresa https://link.springer.com/article/10.1007/s00018-023-04783-y
Počet záznamů: 1