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Bacteriophage PRD1 as a nanoscaffold for drug loading

DOI: 10.1039/D1NR04153C DOI Help

Authors: Helen M. E. Duyvesteyn (University of Oxford; Diamond Light Source) , Isaac Santos-Perez (Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)) , Francesca Peccati (Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)) , Ane Martinez-Castillo (Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)) , Thomas S. Walter (University of Oxford) , David Reguera (Universitat de Barcelona) , Felix M. Goñi (University of the Basque Country (UPV/EHU); Instituto Biofisika (CSIC, UPV/EHU)) , Gonzalo Jiménez-Osés (Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA); IKERBASQUE, Basque Foundation for Science) , Hanna M. Oksanen , David I. Stuart (University of Oxford; Diamond Light Source; Instruct-ERI) , Nicola G. A. Abrescia (Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA); IKERBASQUE, Basque Foundation for Science; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nanoscale , VOL 156

State: Published (Approved)
Published: December 2021
Diamond Proposal Number(s): 14744

Open Access Open Access

Abstract: Viruses are very attractive biomaterials owing to their capability as nanocarriers of genetic material. Efforts have been made to functionalize self-assembling viral protein capsids on their exterior or interior to selectively take up different payloads. PRD1 is a double-stranded DNA bacteriophage comprising an icosahedral protein outer capsid and an inner lipidic vesicle. Here, we report the three-dimensional structure of PRD1 in complex with the antipsychotic drug chlorpromazine (CPZ) by cryo-electron microscopy. We show that the jellyrolls of the viral major capsid protein P3, protruding outwards from the capsid shell, serve as scaffolds for loading heterocyclic CPZ molecules. Additional X-ray studies and molecular dynamics simulations show the binding modes and organization of CPZ molecules when complexed with P3 only and onto the virion surface. Collectively, we provide a proof of concept for the possible use of the lattice-like organisation and the quasi-symmetric morphology of virus capsomers for loading heterocyclic drugs with defined properties.

Diamond Keywords: Viruses; Bacteriophages

Subject Areas: Biology and Bio-materials, Medicine


Instruments: I24-Microfocus Macromolecular Crystallography

Added On: 06/12/2021 13:30

Documents:
d1nr04153c.pdf

Discipline Tags:

Life Sciences & Biotech Health & Wellbeing Drug Delivery Structural biology Nanoscience/Nanotechnology

Technical Tags:

Diffraction Macromolecular Crystallography (MX)