Biosensors Paving the Way to Understanding the Interaction between Cadmium and the Estrogen Receptor Alpha 英文参考文献.docVIP

BiosensorsPavingtheWaytoUnderstandingthe InteractionbetweenCadmiumandtheEstrogen ReceptorAlpha PeterFechner1,PauliinaDamdimopoulou2,Gu¨nterGauglitz1* 1InstituteofPhysicalandTheoreticalChemistry(IPTC),Eberhard-Karls-UniversityofTu¨bingen,Tu¨bingen,Germany,2DepartmentofBiosciencesandNutrition,Karolinska Institutet,Huddinge,Sweden Abstract Cadmiumisatoxicheavymetalubiquitouslypresentintheenvironmentandsubsequentlyinthehumandiet.Cadmium has been proposed to disrupt the endocrine system, targeting in particular the estrogen signaling pathway already at environmentallyrelevantconcentrations.Thusfar,thereportsonthebindingaffinityofcadmiumtowardshumanestrogen receptoralpha(hERa)havebeencontradicting,ashavebeenthereportsontheinvivoestrogenicityofcadmium.Hence, the mode of interaction between cadmium and the receptor remains unclear. Here, we investigated the interaction between cadmium and hERa on a molecular level by applying a novel, label-free biosensor technique based on reflectometricinterferencespectroscopy(RIfS).WestudiedthebindingofcadmiumtohERa,andtheconformationofthe receptorfollowingcadmiumtreatment.Ourdatarevealsthatcadmiuminteractswiththeligandbindingdomain(LBD)of theERaandaffectstheconformationofthereceptor.However,thebindingevent,aswellastheinducedconformation change, greatly depends on the accessibility of the cysteine tails in the LBD. As the LBD cysteine residues have been reportedastargetsofpost-translationalmodificationsinvivo,wepresentahypothesisaccordingtowhichdifferentcellular pools of ERa respond to cadmium differently. Our proposed theory could help to explain some of the previously contradictingresultsregardingestrogen-likeactivityofcadmium. Citation:FechnerP,DamdimopoulouP,GauglitzG(2011)BiosensorsPavingtheWaytoUnderstandingtheInteractionbetweenCadmiumandtheEstrogen ReceptorAlpha.PLoSONE6(8):e23048.doi:10.1371/journal.pone.0023048 Editor:JieZheng,UniversityofAkron,UnitedStatesofAmerica ReceivedApril28,2011;AcceptedJuly5,2011;PublishedAugust2,2011