Single methyl groups can act as toggle switches to specify transmembrane Protein-protein interactions
He L, Steinocher H, Shelar A, Cohen EB, Heim EN, Kragelund BB, Grigoryan G, DiMaio D. Single methyl groups can act as toggle switches to specify transmembrane Protein-protein interactions. ELife 2017, 6: e27701. PMID: 28869036, PMCID: PMC5597333, DOI: 10.7554/elife.27701.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineHumansIsoleucineLeucineMembrane ProteinsMiceProtein BindingProtein MultimerizationReceptors, ErythropoietinSubstrate SpecificityConceptsProtein-protein interactionsErythropoietin receptorTransmembrane proteinTransmembrane protein-protein interactionsTMD interactionsModel transmembrane proteinMouse erythropoietin receptorHuman erythropoietin receptorSingle methyl groupGrowth factor independenceSide chain methyl groupsCellular processesMouse cellsFactor independenceChain methyl groupsIntrinsic specificityToggle switchTraptamersMethyl groupProteinReceptor activitySpecific positionsReceptorsSpecificityOligomerizationTwo transmembrane dimers of the bovine papillomavirus E5 oncoprotein clamp the PDGF β receptor in an active dimeric conformation
Karabadzhak AG, Petti LM, Barrera FN, Edwards APB, Moya-Rodríguez A, Polikanov YS, Freites JA, Tobias DJ, Engelman DM, DiMaio D. Two transmembrane dimers of the bovine papillomavirus E5 oncoprotein clamp the PDGF β receptor in an active dimeric conformation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e7262-e7271. PMID: 28808001, PMCID: PMC5584431, DOI: 10.1073/pnas.1705622114.Peer-Reviewed Original ResearchConceptsTransmembrane domainE5 proteinE5 dimerPlatelet-derived growth factor β receptorGrowth factor β receptorActive dimeric conformationPDGF β-receptorTransmembrane dimerProtein bindsMembrane environmentReceptor dimerizationDimeric conformationAtom molecular dynamics simulationsBiochemical experimentsMouse cellsMolecular mechanismsActive dimerΒ receptorBovine papillomavirusProteinSpecific interactionsMembrane modelingReceptor activationDimerizationComplexes