A structural model of the iRhom-ADAM17 sheddase complex reveals functional insights into its trafficking and activity

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F23%3A00572295" target="_blank" >RIV/68378050:_____/23:00572295 - isvavai.cz</a>
Result on the web
<a href="https://link.springer.com/article/10.1007/s00018-023-04783-y" target="_blank" >https://link.springer.com/article/10.1007/s00018-023-04783-y</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s00018-023-04783-y" target="_blank" >10.1007/s00018-023-04783-y</a>

Result language
angličtina
Original language name
A structural model of the iRhom-ADAM17 sheddase complex reveals functional insights into its trafficking and activity
Original language description
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.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology

Project
<a href="/en/project/LM2018126" target="_blank" >LM2018126: Czech Centre for Phenogenomics</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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