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dc.rights.licenseopenen_US
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorDASKALOV, A.
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorMARTINEZ, D.
hal.structure.identifierInstitut de biochimie et génétique cellulaires [IBGC]
dc.contributor.authorCOUSTOU, V.
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorEL MAMMERI, N.
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorBERBON, Melanie
dc.contributor.authorANDREAS, L. B.
dc.contributor.authorBARDIAUX, B.
dc.contributor.authorSTANEK, J.
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorNOUBHANI, A.
hal.structure.identifierInstitut Européen de Chimie et Biologie [IECB]
dc.contributor.authorKAUFFMANN, B.
dc.contributor.authorWALL, J. S.
dc.contributor.authorPINTACUDA, G.
hal.structure.identifierInstitut de biochimie et génétique cellulaires [IBGC]
dc.contributor.authorSAUPE, S. J.
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorHABENSTEIN, Birgit
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorLOQUET, A.
dc.date.accessioned2021-07-01T12:37:20Z
dc.date.available2021-07-01T12:37:20Z
dc.date.issued2021
dc.identifier.issn0027-8424en_US
dc.identifier.otherhttps://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2014085118/-/DCSupplementalen_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/94956
dc.description.abstractEnNeurodegenerative disorders are frequently associated with beta-sheet-rich amyloid deposits. Amyloid-forming proteins can aggregate under different structural conformations known as strains, which can exhibit a prion-like behavior and distinct pathophenotypes. Precise molecular determinants defining strain specificity and cross-strain interactions (cross-seeding) are currently unknown. The HET-s prion protein from the fungus Podospora anserina represents a model system to study the fundamental properties of prion amyloids. Here, we report the amyloid prion structure of HELLF, a distant homolog of the model prion HET-s. We find that these two amyloids, sharing only 17% sequence identity, have nearly identical beta-solenoid folds but lack cross-seeding ability in vivo, indicating that prion specificity can differ in extremely similar amyloid folds. We engineer the HELLF sequence to explore the limits of the sequence-to-fold conservation and to pinpoint determinants of cross-seeding and prion specificity. We find that amyloid fold conservation occurs even at an exceedingly low level of identity to HET-s (5%). Next, we derive a HELLF-based sequence, termed HEC, able to breach the cross-seeding barrier in vivo between HELLF and HET-s, unveiling determinants controlling cross-seeding at residue level. These findings show that virtually identical amyloid backbone structures might not be sufficient for cross-seeding and that critical side-chain positions could determine the seeding specificity of an amyloid fold. Our work redefines the conceptual boundaries of prion strain and sheds light on key molecular features concerning an important class of pathogenic agents.
dc.language.isoENen_US
dc.subject.enamyloid
dc.subject.enprion
dc.subject.ensequence to fold
dc.subject.encross-seeding
dc.subject.ennuclear magnetic resonance
dc.title.enStructural and molecular basis of cross-seeding barriers in amyloids
dc.typeArticle de revueen_US
dc.identifier.doi10.1073/pnas.2014085118en_US
dc.subject.halChimie/Matériauxen_US
bordeaux.journalProceedings of the National Academy of Sciences of the United States of Americaen_US
bordeaux.volume118en_US
bordeaux.hal.laboratoriesInstitut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN) - UMR 5248en_US
bordeaux.issue1en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionBordeaux INPen_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierpasteur-03106845
hal.exportfalse
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20of%20the%20United%20States%20of%20America&rft.date=2021&rft.volume=118&rft.issue=1&rft.eissn=0027-8424&rft.issn=0027-8424&rft.au=DASKALOV,%20A.&MARTINEZ,%20D.&COUSTOU,%20V.&EL%20MAMMERI,%20N.&BERBON,%20Melanie&rft.genre=article


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