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000139102 0247_ $$2pmid$$apmid:22401494
000139102 0247_ $$2pmc$$apmc:PMC3319454
000139102 0247_ $$2doi$$a10.1021/bi201857v
000139102 0247_ $$2ISSN$$a1520-4995
000139102 0247_ $$2ISSN$$a0006-2960
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000139102 037__ $$aPHPPUBDB-23647
000139102 041__ $$aeng
000139102 082__ $$a570
000139102 1001_ $$aJones, E. M.
000139102 1101_ $$aDESY$$bMax-Planck-Arbeitsgruppen
000139102 245__ $$aInteraction of Tau Protein with Model Lipid Membranes Induces Tau Structural Compaction and Membrane Disruption
000139102 260__ $$aColumbus, Ohio$$bAmerican Chemical Society$$c2012
000139102 300__ $$a2539
000139102 3367_ $$00$$2EndNote$$aJournal Article
000139102 3367_ $$2BibTeX$$aARTICLE
000139102 3367_ $$2DRIVER$$aarticle
000139102 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$mjournal
000139102 440_0 $$0PERI:(DE-600)1472258-6$$aBiochem.$$v51$$x0006-2960$$y12
000139102 500__ $$3Converted on 2013-05-30 09:22
000139102 500__ $$3Converted on 2013-06-21 19:21
000139102 520__ $$aThe misfolding and aggregation of the intrinsically disordered, microtubule-associated tau protein into neurofibrillary tangles is implicated in the pathogenesis of Alzheimer's disease. However, the mechanisms of tau aggregation and toxicity remain unknown. Recent work has shown that anionic lipid membranes can induce tau aggregation and that membrane permeabilization may serve as a pathway by which protein aggregates exert toxicity, suggesting that the plasma membrane may play dual roles in tau pathology. This prompted our investigation to assess tau's propensity to interact with membranes and to elucidate the mutually disruptive structural perturbations the interactions induce in both tau and the membrane. We show that although highly charged and soluble, the full-length tau (hTau40) is also highly surface active, selectively inserts into anionic DMPG lipid monolayers and induces membrane morphological changes. To resolve molecular-scale structural details of hTau40 associated with lipid membranes, X-ray and neutron scattering techniques are utilized. X-ray reflectivity indicates hTau40s presence underneath a DMPG monolayer and penetration into the lipid headgroups and tailgroups, whereas grazing incidence X-ray diffraction shows that hTau40 insertion disrupts lipid packing. Moreover, both air/water and DMPG lipid membrane interfaces induce the disordered hTau40 to partially adopt a more compact conformation with density similar to that of a folded protein. Neutron reflectivity shows that tau completely disrupts supported DMPG bilayers while leaving the neutral DPPC bilayer intact. Our results show that hTau40s strong interaction with anionic lipids induces tau structural compaction and membrane disruption, suggesting possible membrane-based mechanisms of tau aggregation and toxicity in neurodegenerative diseases.
000139102 536__ $$0G:(DE-H253)POF2-BW1-20130405$$aDORIS Beamline BW1 (POF2-54G13)$$cPOF2-54G13$$fPOF II$$x0
000139102 588__ $$aDataset connected to Pubmed
000139102 650_2 $$2MeSH$$aCell Membrane: chemistry
000139102 650_2 $$2MeSH$$aCell Membrane: metabolism
000139102 650_2 $$2MeSH$$aHumans
000139102 650_2 $$2MeSH$$aLipid Bilayers: chemistry
000139102 650_2 $$2MeSH$$aLipid Bilayers: metabolism
000139102 650_2 $$2MeSH$$aNeutron Diffraction
000139102 650_2 $$2MeSH$$aProtein Binding
000139102 650_2 $$2MeSH$$aProtein Conformation
000139102 650_2 $$2MeSH$$aSolubility
000139102 650_2 $$2MeSH$$aX-Ray Diffraction
000139102 650_2 $$2MeSH$$atau Proteins: chemistry
000139102 650_2 $$2MeSH$$atau Proteins: metabolism
000139102 650_7 $$00$$2NLM Chemicals$$aLipid Bilayers
000139102 650_7 $$00$$2NLM Chemicals$$atau Proteins
000139102 693__ $$0EXP:(DE-H253)D-BW1-20150101$$1EXP:(DE-H253)DORISIII-20150101$$6EXP:(DE-H253)D-BW1-20150101$$aDORIS III$$fDORIS Beamline BW1$$x0
000139102 7001_ $$aDubey, M.
000139102 7001_ $$aCamp, P. J.
000139102 7001_ $$aVernon, B. C.
000139102 7001_ $$aBiernat, J.
000139102 7001_ $$aMandelkow, E.
000139102 7001_ $$aMajewski, J.
000139102 7001_ $$aChi, E. Y.
000139102 773__ $$0PERI:(DE-600)1472258-6$$a10.1021/bi201857v$$gVol. 51, p. 2539$$p2539$$q51<2539$$tBiochemistry$$v51$$x0006-2960$$y2012
000139102 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319454
000139102 909CO $$ooai:bib-pubdb1.desy.de:139102$$pVDB
000139102 9101_ $$0I:(DE-HGF)0$$aExternes Institut$$kExtern
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000139102 9141_ $$y2012
000139102 915__ $$0StatID:(DE-HGF)0010$$aJCR/ISI refereed
000139102 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aMedline
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000139102 980__ $$aConvertedRecord