PuSH - Publikationsserver des Helmholtz Zentrums München

Harati Taji, Z. ; Bielytskyi, P. ; Shein, M. ; Sani, M.A.* ; Seitz, S.* ; Schütz, A.K.

Transient RNA interactions leave a covalent imprint on a viral capsid protein.

J. Am. Chem. Soc. 144, 8536-8550 (2022)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
The hepatitis B virus (HBV) is the leading cause of persistent liver infections. Its DNA-based genome is synthesized through reverse transcription of an RNA template inside the assembled capsid shell. In addition to the structured assembly domain, the capsid protein harbors a C-terminal extension that mediates both the enclosure of RNA during capsid assembly and the nuclear entry of the capsid during infection. The arginine-rich motifs within this extension, though common to many viruses, have largely escaped atomic-scale investigation. Here, we leverage solution and solid-state nuclear magnetic resonance spectroscopy at ambient and cryogenic temperatures, under dynamic nuclear polarization signal enhancement, to investigate the organization of the genome within the capsid. Transient interactions with phosphate groups of the RNA backbone confine the arginine-rich motifs to the interior capsid space. While no secondary structure is induced in the C-terminal extension, interactions with RNA counteract the formation of a disulfide bond, which covalently tethers this peptide arm onto the inner capsid surface. Electrostatic and covalent contributions thus compete in the spatial regulation of capsid architecture. This disulfide switch represents a coupling mechanism between the structured assembly domain of the capsid and the enclosed nucleic acids. In particular, it enables the redox-dependent regulation of the exposure of the C-terminal extension on the capsid surface, which is required for nuclear uptake of the capsid. Phylogenetic analysis of capsid proteins from hepadnaviruses points toward a function of this switch in the persistence of HBV infections.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
ISSN (print) / ISBN 0002-7863
e-ISSN 1520-5126
Zeitschrift Journal of the American Chemical Society
Quellenangaben Band: 144, Heft: 19, Seiten: 8536-8550 Artikelnummer: , Supplement: ,
Verlag American Chemical Society (ACS)
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Structural Biology (STB)
Förderungen Helmholtz Association
Deutsche Forschungsgemeinschaft
Australian Research Council