Two transmembrane dimers of the bovine papillomavirus E5 oncoprotein clamp the PDGF ß receptor in an active dimeric conformation.
Proc Natl Acad Sci U S A
; 114(35): E7262-E7271, 2017 08 29.
Article
de En
| MEDLINE
| ID: mdl-28808001
ABSTRACT
The dimeric 44-residue E5 protein of bovine papillomavirus is the smallest known naturally occurring oncoprotein. This transmembrane protein binds to the transmembrane domain (TMD) of the platelet-derived growth factor ß receptor (PDGFßR), causing dimerization and activation of the receptor. Here, we use Rosetta membrane modeling and all-atom molecular dynamics simulations in a membrane environment to develop a chemically detailed model of the E5 protein/PDGFßR complex. In this model, an active dimer of the PDGFßR TMD is sandwiched between two dimers of the E5 protein. Biochemical experiments showed that the major PDGFßR TMD complex in mouse cells contains two E5 dimers and that binding the PDGFßR TMD to the E5 protein is necessary and sufficient to recruit both E5 dimers into the complex. These results demonstrate how E5 binding induces receptor dimerization and define a molecular mechanism of receptor activation based on specific interactions between TMDs.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Protéines des oncogènes viraux
/
Récepteur au PDGF bêta
Type d'étude:
Prognostic_studies
Limites:
Animals
/
Humans
Langue:
En
Journal:
Proc Natl Acad Sci U S A
Année:
2017
Type de document:
Article