title: Tailored protein encapsulation into a DNA host using geometrically organized supramolecular interactions.
abstract: The self-organizational properties of DNA have been used to realize synthetic hosts for protein encapsulation. However, current strategies of DNA-protein conjugation still limit true emulation of natural host-guest systems, whose formation relies on non-covalent bonds between geometrically matching interfaces. Here we report one of the largest DNA-protein complexes of semisynthetic origin held in place exclusively by spatially defined supramolecular interactions. Our approach is based on the decoration of the inner surface of a DNA origami hollow structure with multiple ligands converging to their corresponding binding sites on the protein surface with programmable symmetry and range-of-action. Our results demonstrate specific host-guest recognition in a 1:1 stoichiometry and selectivity for the guest whose size guarantees sufficient molecular diffusion preserving short intermolecular distances. DNA nanocontainers can be thus rationally designed to trap single guest molecules in their native form, mimicking natural strategies of molecular recognition and anticipating a new method of protein caging.
authors.affiliation: Centre for Medical Biotechnology (ZMB), Centre for Nano Integration Duisburg-Essen, University of Duisburg-Essen, Universitätstrasse 2, Essen 45117, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Sprengel
authors.affiliation: Department of Structural Biochemistry, Max-Planck-Institute of Molecular Physiology, Otto-Hahn-Straße 11, Dortmund 44227, Germany.
authors.forename: Pascal
authors.initials: P
authors.lastname: Lill
authors.affiliation: Centre for Medical Biotechnology (ZMB), Centre for Nano Integration Duisburg-Essen, University of Duisburg-Essen, Universitätstrasse 2, Essen 45117, Germany.
authors.forename: Pierre
authors.initials: P
authors.lastname: Stegemann
authors.affiliation: Theory Department, Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, Mülheim an der Ruhr 45470, Germany.
authors.forename: Kenny
authors.initials: K
authors.lastname: Bravo-Rodriguez
authors.affiliation: Centre for Medical Biotechnology (ZMB), Centre for Nano Integration Duisburg-Essen, University of Duisburg-Essen, Universitätstrasse 2, Essen 45117, Germany.
authors.forename: Elisa-C
authors.initials: EC
authors.lastname: Schöneweiß
authors.affiliation: Centre for Medical Biotechnology (ZMB), Centre for Nano Integration Duisburg-Essen, University of Duisburg-Essen, Universitätstrasse 2, Essen 45117, Germany.
authors.forename: Melisa
authors.initials: M
authors.lastname: Merdanovic
authors.affiliation: Department of Chemistry and Interdisciplinary Nanoscience Center, Aarhus University, Gustav Wieds Vej 14, Aarhus 8000, Denmark.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gudnason
authors.affiliation: Department of Chemistry and Interdisciplinary Nanoscience Center, Aarhus University, Gustav Wieds Vej 14, Aarhus 8000, Denmark.
authors.forename: Mikayel
authors.identifier: 0000-0002-5395-3441
authors.initials: M
authors.lastname: Aznauryan
authors.affiliation: Centre for Medical Biotechnology (ZMB), Centre for Nano Integration Duisburg-Essen, University of Duisburg-Essen, Universitätstrasse 2, Essen 45117, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Gamrad
authors.affiliation: Centre for Medical Biotechnology (ZMB), Centre for Nano Integration Duisburg-Essen, University of Duisburg-Essen, Universitätstrasse 2, Essen 45117, Germany.
authors.forename: Stephan
authors.identifier: 0000-0002-9739-7272
authors.initials: S
authors.lastname: Barcikowski
authors.affiliation: Theory Department, Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, Mülheim an der Ruhr 45470, Germany.
authors.forename: Elsa
authors.initials: E
authors.lastname: Sanchez-Garcia
authors.affiliation: Department of Chemistry and Interdisciplinary Nanoscience Center, Aarhus University, Gustav Wieds Vej 14, Aarhus 8000, Denmark.
authors.forename: Victoria
authors.initials: V
authors.lastname: Birkedal
authors.affiliation: Department of Structural Biochemistry, Max-Planck-Institute of Molecular Physiology, Otto-Hahn-Straße 11, Dortmund 44227, Germany.
authors.forename: Christos
authors.initials: C
authors.lastname: Gatsogiannis
authors.affiliation: Centre for Medical Biotechnology (ZMB), Centre for Nano Integration Duisburg-Essen, University of Duisburg-Essen, Universitätstrasse 2, Essen 45117, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Ehrmann
authors.affiliation: Centre for Medical Biotechnology (ZMB), Centre for Nano Integration Duisburg-Essen, University of Duisburg-Essen, Universitätstrasse 2, Essen 45117, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Saccà
mesh_terms: D001665:Binding Sites; D060326:Chemistry Techniques, Synthetic; D004247:DNA / Q000737:chemistry*; D005818:Genetic Engineering; D006360:Heat-Shock Proteins / Q000737:chemistry* / Q000235:genetics; D008024:Ligands; D008958:Models, Molecular; D057054:Molecular Imaging; D015335:Molecular Probes; D015394:Molecular Structure; D033903:Periplasmic Proteins / Q000737:chemistry* / Q000235:genetics; D011108:Polymers / Q000737:chemistry; D054730:Protein Interaction Domains and Motifs; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000235:genetics
chemical_list: D006360:Heat-Shock Proteins; D008024:Ligands; D015335:Molecular Probes; D033903:Periplasmic Proteins; D011108:Polymers; D004247:DNA; C061682:DegP protease; D012697:Serine Endopeptidases