2024
De novo-designed transmembrane proteins bind and regulate a cytokine receptor
Mravic M, He L, Kratochvil H, Hu H, Nick S, Bai W, Edwards A, Jo H, Wu Y, DiMaio D, DeGrado W. De novo-designed transmembrane proteins bind and regulate a cytokine receptor. Nature Chemical Biology 2024, 20: 751-760. PMID: 38480980, PMCID: PMC11142920, DOI: 10.1038/s41589-024-01562-z.Peer-Reviewed Original ResearchTM proteinsTM regionTarget membrane proteinsComplex biological functionsTM domainTM helicesInteraction partnersTransmembrane proteinsMembrane proteinsReceptor homodimerizationBiological functionsCytokine receptorsBinding topologyAmino acidsProteinErythropoietin receptorHomodimerizationCell proliferationTransmembraneEpoRIn vitroMolecular modelingBinding modeReceptorsMotif
2023
Allosteric inhibition of the T cell receptor by a designed membrane ligand
Ye Y, Morita S, Chang J, Buckley P, Wilhelm K, DiMaio D, Groves J, Barrera F. Allosteric inhibition of the T cell receptor by a designed membrane ligand. ELife 2023, 12: e82861. PMID: 37796108, PMCID: PMC10554751, DOI: 10.7554/elife.82861.Peer-Reviewed Original ResearchConceptsT cell receptorTCR activationCD3ζ subunitsTM ligandsComplex molecular machinesReceptor tyrosine kinase EphA2Cell receptorTM domainTransmembrane domainNative nanodiscsTCR subunitsAllosteric changesTM bundleCytoplasmic sideTM regionMolecular mechanismsExtracellular domainAllosteric inhibitionLck phosphorylationMolecular machinesMembrane receptorsAberrant activationSubunitsMembrane ligandsDecades of investigation
2022
Human Papillomavirus L2 Capsid Protein Stabilizes γ-Secretase during Viral Infection
Crite M, DiMaio D. Human Papillomavirus L2 Capsid Protein Stabilizes γ-Secretase during Viral Infection. Viruses 2022, 14: 804. PMID: 35458534, PMCID: PMC9027364, DOI: 10.3390/v14040804.Peer-Reviewed Original ResearchConceptsTM domainΓ-secretaseVirus traffickingCellular transmembrane proteinsNon-canonical rolePutative TM domainRetrograde transport pathwayΓ-secretase complexSubstrate proteinsMinor capsid protein L2Transmembrane proteinCatalytic subunitMutational studiesEndosomal membranesIntracellular traffickingProtein L2Cellular proteasesCellular factorsL2 capsid proteinsTM mutantsCapsid proteinHPV entryTraffickingL2 proteinProtein