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Engineering an AB₅ Protein Carrier

URN to cite this document: urn:nbn:de:bvb:703-epub-4244-7

Title data

Lichtenstein, Bruce R. ; Höcker, Birte:
Engineering an AB₅ Protein Carrier.
In: Scientific Reports. Vol. 2018 (23 August 2018) Issue 8 . - No. 12643.
ISSN 2045-2322
DOI der Verlagsversion: https://doi.org/10.1038/s41598-018-30910-y

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Abstract

The promise of biologic therapeutics is hindered by the challenge to deliver their activity to biochemically relevant sites within diseased cells. The favourable application of the natural protein carriers of the AB₅ toxin family to this challenge has been restricted owing to still unresolved requirements for assembling non-native cargo into carrier complexes. Here, we clarify the properties of fusion peptides which allow co-assembly of a selected fluorescent protein cargo with the non-toxic B subunit of a heat-labile enterotoxin. We establish the influence of sequence length, sequence identity and secondary structure of these linking domains on the assembly and disassembly of the complexes. Through our engineering framework we identify several non-native, reduced length fusion sequences that robustly assemble with the native carriers, maintain their ability to deliver protein cargo to cells, and demonstrate substantially refined in vitro properties. Constructs based upon these sequences should prove directly applicable to a variety of protein delivery challenges, and the described design framework should find immediate application to other members of the AB₅ protein carrier family.

Further data

Item Type: Article in a journal
Keywords: protein carrier; AB5 toxin family
DDC Subjects: 500 Science
Institutions of the University: Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry III - Protein Design > Chair Biochemistry III - Protein Design - Univ.-Prof. Dr. Birte Höcker
Faculties
Faculties > Faculty of Biology, Chemistry and Earth Sciences
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry I - Proteinbiochemie der Signaltransduktion
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry III - Protein Design
Language: English
Originates at UBT: Yes
URN: urn:nbn:de:bvb:703-epub-4244-7
Date Deposited: 27 Feb 2019 15:29
Last Modified: 07 Jul 2020 10:47
URI: https://epub.uni-bayreuth.de/id/eprint/4244

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