The iRhom homology domain is indispensable for ADAM17-mediated TNF alpha and EGF receptor ligand release
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F21%3A00544132" target="_blank" >RIV/68378050:_____/21:00544132 - isvavai.cz</a>
Result on the web
<a href="https://link.springer.com/article/10.1007/s00018-021-03845-3" target="_blank" >https://link.springer.com/article/10.1007/s00018-021-03845-3</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s00018-021-03845-3" target="_blank" >10.1007/s00018-021-03845-3</a>
Alternative languages
Result language
angličtina
Original language name
The iRhom homology domain is indispensable for ADAM17-mediated TNF alpha and EGF receptor ligand release
Original language description
Membrane-tethered signalling proteins such as TNF alpha and many EGF receptor ligands undergo shedding by the metalloproteinase ADAM17 to get released. The pseudoproteases iRhom1 and iRhom2 are important for the transport, maturation and activity of ADAM17. Yet, the structural and functional requirements to promote the transport of the iRhom-ADAM17 complex have not yet been thoroughly investigated. Utilising in silico and in vitro methods, we here map the conserved iRhom homology domain (IRHD) and provide first insights into its structure and function. By focusing on iRhom2, we identified different structural and functional factors within the IRHD. We found that the structural integrity of the IRHD is a key factor for ADAM17 binding. In addition, we identified a highly conserved motif within an unstructured region of the IRHD, that, when mutated, restricts the transport of the iRhom-ADAM17 complex through the secretory pathway in in vitro, ex vivo and in vivo systems and also increases the half-life of iRhom2 and ADAM17. Furthermore, the disruption of this IRHD motif was also reflected by changes in the yet undescribed interaction profile of iRhom2 with proteins involved in intracellular vesicle transport. Overall, we provide the first insights into the forward trafficking of iRhoms which is critical for TNF alpha and EGF receptor signalling.
Czech name
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Czech description
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Classification
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
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cellular and Molecular Life Sciences
ISSN
1420-682X
e-ISSN
1420-9071
Volume of the periodical
78
Issue of the periodical within the volume
11
Country of publishing house
CH - SWITZERLAND
Number of pages
26
Pages from-to
5015-5040
UT code for WoS article
000647519000003
EID of the result in the Scopus database
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