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Published VersionCC BY-NC-ND V4.0, Open Access
Journal article
ScrepYard: An online resource for disulfide-stabilized tandem repeat peptides
Protein Science, Vol.32(2), pp.1-12
2023
PMID: 36644825
Abstract
Receptor avidity through multivalency is a highly sought-after property of ligands. While readily available in nature in the form of bivalent antibodies, this property remains challenging to engineer in synthetic molecules. The discovery of several bivalent venom peptides containing two homologous and independently folded domains (in a tandem repeat arrangement) has provided a unique opportunity to better understand the underpinning design of multivalency in multimeric biomolecules, as well as how naturally occurring multivalent ligands can be identified. In previous work, we classified these molecules as a larger class termed secreted cysteine rich repeat proteins (SCREPs). Here, we present an online resource; ScrepYard, designed to assist researchers in identification of SCREP sequences of interest and to aid in characterizing this emerging class of biomolecules. Analysis of sequences within the ScrepYard reveals that two domain tandem repeats constitute the most abundant SCREP domain architecture, while the interdomain "linker" regions connecting the functional domains are found to be abundant in amino acids with short or polar sidechains and contain an unusually high abundance of proline residues. Finally, we demonstrate the utility of ScrepYard as a virtual screening tool for discovery of putatively multivalent peptides, by using it as a resource to identify a previously uncharacterized serine protease inhibitor and confirm its predicted activity using an enzyme assay.
Details
- Title
- ScrepYard: An online resource for disulfide-stabilized tandem repeat peptides
- Authors
- Junyu Liu (Author) - The University of QueenslandMichael Maxwell (Author) - The University of QueenslandThom Cuddihy (Author) - The University of QueenslandTheo Crawford (Author) - The University of QueenslandMadeline Bassetti (Author) - The University of QueenslandCameron Hyde (Author) - University of the Sunshine Coast, Queensland, School of Science, Technology and EngineeringSteve Peigneur (Author) - KU LeuvenJan Tytgat (Author) - KU LeuvenEivind A B Undheim (Author) - The University of QueenslandMehdi Mobli (Corresponding Author) - The University of Queensland
- Publication details
- Protein Science, Vol.32(2), pp.1-12
- Publisher
- Wiley-Blackwell Publishing, Inc.
- Date published
- 2023
- DOI
- 10.1002/pro.4566
- ISSN
- 1469-896X; 0961-8368
- PMID
- 36644825
- Copyright note
- This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
- Grant note
- 12W7822N / Fonds Wetenschappelijk Onderzoek; GOA4919N / Fonds Wetenschappelijk Onderzoek; GOC2319N / Fonds Wetenschappelijk Onderzoek; GOE7120N / Fonds Wetenschappelijk Onderzoek; 287462 / Norges Forskningsråd; PDM/19/164 / Katholieke Universiteit Leuven
- Organisation Unit
- School of Education and Tertiary Access; School of Science, Technology and Engineering
- Language
- English
- Record Identifier
- 99706098502621
- Output Type
- Journal article
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