A Hexameric Peptide Barrel as Building Block of Amyloid-β Protofibrils

Lendel, ChristoferDepartment of Chemistry and Biotechnology, Swedish University of Agricultural Sciences (SLU) (author)

Godkänd; 2014; 20140930 (andbra)
Oligomeric and protofibrillar aggregates formed by the amyloid-β peptide (Aβ) are believed to be involved in the pathology of Alzheimer’s disease. Central to Alzheimer pathology is also the fact that the longer Aβ42 peptide is more prone to aggregation than the more prevalent Aβ40. Detailed structural studies of Aβ oligomers and protofibrils have been impeded by aggregate heterogeneity and instability. We previously engineered a variant of Aβ that forms stable protofibrils and here we use solid-state NMR spectroscopy and molecular modeling to derive a structural model of these. NMR data are consistent with packing of residues 16 to 42 of Aβ protomers into hexameric barrel-like oligomers within the protofibril. The core of the oligomers consists of all residues of the central and C-terminal hydrophobic regions of Aβ, and hairpin loops extend from the core. The model accounts for why Aβ42 forms oligomers and protofibrils more easily than Aβ40.

Bjerring, MortenDepartment of Chemistry and Biotechnology, Swedish University of Agricultural Sciences (SLU) (author)
Dubnovitsky, AnatolyDepartment of Chemistry and Biotechnology, Swedish University of Agricultural Sciences (SLU) (author)
Kelly, Robert T.Department of Physics, Warwick University, Coventry (author)
Filippov, AndreiLuleå tekniska universitet,Kemiteknik(Swepub:ltu)andfil (author)
Antzutkin, OlegLuleå tekniska universitet,Kemiteknik(Swepub:ltu)olan (author)
Nielsen, Niels Chr.Center for Insoluble Protein Structures (inSPIN), Interdisciplinary Nanoscience Center (iNANO) and Department of Chemistry, Aarhus University (author)
Härd, TorleifDepartment of Chemistry and Biotechnology, Swedish University of Agricultural Sciences (SLU) (author)
Department of Chemistry and Biotechnology, Swedish University of Agricultural Sciences (SLU)Department of Physics, Warwick University, Coventry (creator_code:org_t)

By the author/editor: Lendel, Christof ...; Bjerring, Morten; Dubnovitsky, Ana ...; Kelly, Robert T.; Filippov, Andrei; Antzutkin, Oleg; show more...; Nielsen, Niels C ...; Härd, Torleif; show less...

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Chemical Science ...; and Physical Chemist ...

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