Featured Publications
Structures of ligand-occupied β-Klotho complexes reveal a molecular mechanism underlying endocrine FGF specificity and activity
Kuzina ES, Ung PM, Mohanty J, Tome F, Choi J, Pardon E, Steyaert J, Lax I, Schlessinger A, Schlessinger J, Lee S. Structures of ligand-occupied β-Klotho complexes reveal a molecular mechanism underlying endocrine FGF specificity and activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 7819-7824. PMID: 30944224, PMCID: PMC6475419, DOI: 10.1073/pnas.1822055116.Peer-Reviewed Original ResearchConceptsFGF receptorsPleiotropic cellular responsesFibroblast growth factor (FGF) familyPrimary high-affinity receptorsKlotho proteinChimeric mutantsGrowth factor familyCatalytic subunitFGFR functionRegulatory interactionsTerminal tailPleiotropic cellular effectsFactor familyP motifS motifExtracellular domainMolecular mechanismsIntracellular signalingCellular responsesSame binding siteCellular effectsGeneral mechanismEndocrine FGFsBinary complexBinding sitesInhibition of ErbB3 by a monoclonal antibody that locks the extracellular domain in an inactive configuration
Lee S, Greenlee EB, Amick JR, Ligon GF, Lillquist JS, Natoli EJ, Hadari Y, Alvarado D, Schlessinger J. Inhibition of ErbB3 by a monoclonal antibody that locks the extracellular domain in an inactive configuration. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 13225-13230. PMID: 26460020, PMCID: PMC4629334, DOI: 10.1073/pnas.1518361112.Peer-Reviewed Original ResearchConceptsAllosteric mechanismExtracellular domainUnique allosteric mechanismFormation of heterodimersReceptor tyrosine kinasesEGF receptor familyTyrosine kinase domainStructure-based designPseudo-kinaseKinase domainLigand-dependent mechanismInactive conformationTyrosine kinaseInactive configurationReceptor familyFamily activationErbB3 activationErbB3KinaseErbB2ErbB4Family membersDomainActivationHeterodimerization
2011
Crystal structure of amyloid precursor-like protein 1 and heparin complex suggests a dual role of heparin in E2 dimerization
Xue Y, Lee S, Ha Y. Crystal structure of amyloid precursor-like protein 1 and heparin complex suggests a dual role of heparin in E2 dimerization. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 16229-16234. PMID: 21930949, PMCID: PMC3182750, DOI: 10.1073/pnas.1103407108.Peer-Reviewed Original ResearchMeSH KeywordsAmyloid beta-Protein PrecursorCrystallography, X-RayDimerizationHeparinModels, MolecularProtein BindingProtein Conformation
2008
Backbone structure of a small helical integral membrane protein: A unique structural characterization
Page RC, Lee S, Moore JD, Opella SJ, Cross TA. Backbone structure of a small helical integral membrane protein: A unique structural characterization. Protein Science 2008, 18: 134-146. PMID: 19177358, PMCID: PMC2708045, DOI: 10.1002/pro.24.Peer-Reviewed Original ResearchConceptsIntegral membrane proteinsSmall integral membrane proteinMembrane proteinsHelical integral membrane proteinsBackbone structureThree-dimensional backbone structureStructural characterizationTransmembrane helix proteinMembrane-mimetic environmentsAmino acid sequenceSolution NMR spectroscopyStructure determination approachChemical shift indexParamagnetic relaxation enhancementHelix proteinsTransmembrane domainExtramembranous domainsMembrane mimeticsMimetic environmentsStructural biologyDihedral restraintsGlobal foldAcid sequenceNMR spectroscopyOrientational restraints
2003
Structure and dynamics of a membrane protein in micelles from three solution NMR experiments
Lee S, Mesleh MF, Opella SJ. Structure and dynamics of a membrane protein in micelles from three solution NMR experiments. Journal Of Biomolecular NMR 2003, 26: 327-334. PMID: 12815259, DOI: 10.1023/a:1024047805043.Peer-Reviewed Original ResearchConceptsMembrane proteinsSolution NMR experimentsPISA wheelsLoop regionDipolar wavesResidual dipolar couplingsBackbone amide resonancesPf1 coat proteinHigh-throughput structural characterizationHeteronuclear NOE experimentsMembrane-bound formHydrophobic helicesHMQC-NOESY experimentsAmphipathic helixCoat proteinNMR experimentsMobile residuesHelical residuesBackbone dynamicsChemical shift anisotropyProteinAmide resonancesHelixResidual chemical shift anisotropyDipolar couplings
1999
Solution structure of neuromedin B by 1H nuclear magnetic resonance spectroscopy
Lee S, Kim Y. Solution structure of neuromedin B by 1H nuclear magnetic resonance spectroscopy. FEBS Letters 1999, 460: 263-269. PMID: 10544247, DOI: 10.1016/s0014-5793(99)01346-0.Peer-Reviewed Original ResearchConceptsNuclear magnetic resonance spectroscopySDS micellesMagnetic resonance spectroscopyTwo-dimensional nuclear magnetic resonance spectroscopyResonance spectroscopyAromatic ring protonsSolution structureMembrane-mimicking environmentHydrophobic acyl chainsStructure-activity relationshipsMethylene protonsLongitudinal relaxation dataNOESY experimentsHelical conformationConformational featuresRing protonsMicellesMolecular mechanismsSpectroscopyAcyl chainsExtrinsic interactionsRelaxation dataEfficient drugsResiduesProtons