Salmonella-based platform for efficient delivery of functional binding proteins to the cytosol

Autor: Daniel Strebinger, Terence H. Rabbitts, Shane J. F. Cronin, Jiri Wald, Francesca Macaluso, Antoine Chabloz, Josef M. Penninger, Thomas C. Marlovits, Ivona Kozieradzki, Andreas Plückthun, Jonas V. Schaefer
Přispěvatelé: University of Zurich, Marlovits, Thomas C, Penninger, Josef M
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Salmonella typhimurium
metabolism [Recombinant Proteins]
Medicine (miscellaneous)
genetics [Carrier Proteins]
law.invention
Type three secretion system
0302 clinical medicine
Cytosol
law
Type III Secretion Systems
lcsh:QH301-705.5
metabolism [Type III Secretion Systems]
Effector
Chemistry
2701 Medicine (miscellaneous)
Cancer metabolism
Recombinant Proteins
Cell biology
Neoplasm Proteins
genetics [Recombinant Proteins]
030220 oncology & carcinogenesis
metabolism [Neoplasm Proteins]
Recombinant DNA
General Agricultural and Biological Sciences
Intracellular
genetics [Bacterial Proteins]
metabolism [Bacterial Proteins]
610 Medicine & health
1100 General Agricultural and Biological Sciences
genetics [Salmonella typhimurium]
DNA-binding protein
General Biochemistry
Genetics and Molecular Biology

Article
Applied microbiology
03 medical and health sciences
Bacterial Proteins
1300 General Biochemistry
Genetics and Molecular Biology

ddc:570
10019 Department of Biochemistry
Humans
Secretion
growth & development [Salmonella typhimurium]
genetics [Neoplasm Proteins]
Protein transport
Molecular engineering
Protein delivery
HCT116 Cells
030104 developmental biology
genetics [Type III Secretion Systems]
Ras Signaling Pathway
lcsh:Biology (General)
570 Life sciences
biology
metabolism [Cytosol]
metabolism [Salmonella typhimurium]
Carrier Proteins
metabolism [Carrier Proteins]
HeLa Cells
Zdroj: Communications biology 3(1), 342 (2020). doi:10.1038/s42003-020-1072-4
Communications Biology, Vol 3, Iss 1, Pp 1-11 (2020)
Communications Biology
DOI: 10.1038/s42003-020-1072-4
Popis: Communications biology 3(1), 342 (2020). doi:10.1038/s42003-020-1072-4
Protein-based affinity reagents (like antibodies or alternative binding scaffolds) offer wide-ranging applications for basic research and therapeutic approaches. However, whereas small chemical molecules efficiently reach intracellular targets, the delivery of macromolecules into the cytosol of cells remains a major challenge; thus cytosolic applications of protein-based reagents are rather limited. Some pathogenic bacteria have evolved a conserved type III secretion system (T3SS) which allows the delivery of effector proteins into eukaryotic cells. Here, we enhance the T3SS of an avirulent strain of Salmonella typhimurium to reproducibly deliver multiple classes of recombinant proteins into eukaryotic cells. The efficacy of the system is probed with both DARPins and monobodies to functionally inhibit the paradigmatic and largely undruggable RAS signaling pathway. Thus, we develop a bacterial secretion system for potent cytosolic delivery of therapeutic macromolecules.
Published by Springer Nature, London
Databáze: OpenAIRE