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Increased stability of the TM helix oligomer abrogates the apoptotic activity of the human Fas receptor
- Source :
- Biochimica et Biophysica Acta (BBA) - Biomembranes. 1864:183807
- Publication Year :
- 2022
- Publisher :
- Elsevier BV, 2022.
-
Abstract
- Human death receptors control apoptotic events during cell differentiation, cell homeostasis and the elimination of damaged or infected cells. Receptor activation involves ligand-induced structural reorganizations of preformed receptor trimers. Here we show that the death receptor transmembrane domains only have a weak intrinsic tendency to homo-oligomerize within a membrane, and thus these domains potentially do not significantly contribute to receptor trimerization. However, mutation of Pro183 in the human CD95/Fas receptor transmembrane helix results in a dramatically increased interaction propensity, as shown by genetic assays. The increased interaction of the transmembrane domain is coupled with a decreased ligand-sensitivity of cells expressing the Fas receptor, and thus in a decreased number of apoptotic events. Mutation of Pro183 likely results in a substantial rearrangement of the self-associated Fas receptor transmembrane trimer, which likely abolishes further signaling of the apoptotic signal but may activate other signaling pathways. Our study shows that formation of a stable Fas receptor transmembrane helix oligomer does not per se result in receptor activation.
- Subjects :
- Cellular differentiation
Biophysics
Apoptosis
Ligands
medicine.disease_cause
Biochemistry
Protein Domains
medicine
Homeostasis
Humans
fas Receptor
Receptor
Mutation
Chemistry
Cell Differentiation
Receptors, Death Domain
Cell Biology
Fas receptor
Transmembrane protein
Cell biology
Transmembrane domain
Protein Multimerization
Signal transduction
Signal Transduction
Subjects
Details
- ISSN :
- 00052736
- Volume :
- 1864
- Database :
- OpenAIRE
- Journal :
- Biochimica et Biophysica Acta (BBA) - Biomembranes
- Accession number :
- edsair.doi.dedup.....676f68d40d2c4d7cb52215686648ab46