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The role of metals in protein conformational disorders - The case of prion protein and Aβ -peptide

机译:金属在蛋白质构象疾病中的作用-ion病毒蛋白和Aβ肽的情况

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摘要

Proteinconformationaldisordersaremembersofavastclassofpathologiesinwhichendogenousproteinsorpeptidesundergoamisfoldingprocessbyswitchingfromthephysiologicalsolubleconfigurationtoapathologicalfibrillarinsolublestate.Animportant,butnotyetfullyelucidated,roleintheprocessappearstobeplayedbytransitionmetalions,mainlycopperandzinc.X-rayabsorptionspectroscopyisoneofthemostsuitabletechniquesforthestructuralcharacterizationofbiologicalmoleculesincomplexwithmetal.Owingtoitschemicalselectivityandsensitivitytothelocalatomicgeometryaroundtheabsorber,itcanbesuccessfullyusedtostudytheenvironmentofmetalionsincomplexwithproteinsandpeptidesinphysiologicalconditions.InthispaperwepresentX-rayabsorptionspectroscopystudiesofthemetalionscoordinationmodesinsystemswheremetalsarecomplexedwithspecificamyloidogenicproteinsandpeptides.Inparticular,weshowresultsconcerningtheAmyloidβpeptide,thatisinvolvedinAlzheimer'sdisease,andthePrionprotein,thatisresponsiblefortheTransmissibleSpongiformEncephalopathy.Ourfindingssuggestthatthecopperandzincionsmayplayacrucialroleintheaggregationandfibrilformationprocessofthesetwobiomolecules.Elucidatingthiskindofinteractioncouldbeakeypreliminarystepbeforeanyviabletherapycanbeconceivedordesigned...
机译:Proteinconformationaldisordersaremembersofavastclassofpathologiesinwhichendogenousproteinsorpeptidesundergoamisfoldingprocessbyswitchingfromthephysiologicalsolubleconfigurationtoapathologicalfibrillarinsolublestate.Animportant,butnotyetfullyelucidated,roleintheprocessappearstobeplayedbytransitionmetalions,mainlycopperandzinc.X-rayabsorptionspectroscopyisoneofthemostsuitabletechniquesforthestructuralcharacterizationofbiologicalmoleculesincomplexwithmetal.Owingtoitschemicalselectivityandsensitivitytothelocalatomicgeometryaroundtheabsorber,itcanbesuccessfullyusedtostudytheenvironmentofmetalionsincomplexwithproteinsandpeptidesinphysiologicalconditions.InthispaperwepresentX-rayabsorptionspectroscopystudiesofthemetalionscoordinationmodesinsystemswheremetalsarecomplexedwithspecificamyloidogenicproteinsandpeptides.Inparticular,weshowresultsconcerningtheAmyloidβpeptide,thatisinvolvedinAlzheimer'sdisease,andthePrionprotein,thatisresponsiblefortheTransmissibleSpongiformEncephalopathy.Ourfindingss这表明铜和锌可能会在这两种生物分子的聚集和原纤维形成过程中发挥作用。阐明这种相互作用的类型可以作为任何可行的治疗方法的关键的初步步骤。

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