A1 Refereed original research article in a scientific journal

HIV Tat protein and amyloid-beta peptide form multifibrillar structures that cause neurotoxicity




AuthorsHategan A, Bianchet MA, Steiner J, Karnaukhova E, Masliah E, Fields A, Lee MH, Dickens AM, Haughey N, Dimitriadis EK, Nath A

PublisherNATURE PUBLISHING GROUP

Publication year2017

JournalNature Structural and Molecular Biology

Journal name in sourceNATURE STRUCTURAL & MOLECULAR BIOLOGY

Journal acronymNAT STRUCT MOL BIOL

Volume24

Issue4

First page 379

Last page389

Number of pages11

ISSN1545-9993

DOIhttps://doi.org/10.1038/nsmb.3379(external)


Abstract
Deposition of amyloid-beta plaques is increased in the brains of HIV-infected individuals, and the HIV transactivator of transcription (Tat) protein affects amyloidogenesis through several indirect mechanisms. Here, we investigated direct interactions between Tat and amyloid-beta peptide. Our in vitro studies showed that in the presence of Tat, uniform amyloid fibrils become double twisted fibrils and further form populations of thick unstructured filaments and aggregates. Specifically, Tat binding to the exterior surfaces of the A. fibrils increases beta-sheet formation and lateral aggregation into thick multifibrillar structures, thus producing fibers with increased rigidity and mechanical resistance. Furthermore, Tat and A. aggregates in complex synergistically induced neurotoxicity both in vitro and in animal models. Increased rigidity and mechanical resistance of the amyloid-beta-Tat complexes coupled with stronger adhesion due to the presence of Tat in the fibrils may account for increased damage, potentially through pore formation in membranes.



Last updated on 2024-26-11 at 16:31