About SCREPs
Secreted Cysteine-rich REpeat Peptides (SCREPs) [1] are a class of peptides containing multiple homologous domains, and thereby primed for multivalency. In filtering the ever expanding sequence space covered by UniProtKB we have created a database suitable for automated annotation of various properties of significance to protein engineering and the pharmacology of these peptides.
In short, SCREPs are an elaboration on single domain disulfide rich peptides (DRPs), exhibiting many of the same advantages but with added multivalency. Single domain DRPs are themselves of interest as drug leads and pharmacological tools due to their high in vivo stability, demonstrating the capacity for selective and potent activity. Our interest in multi-domain DRPs was inspired by reports of venom derived double-domain peptides. Such examples include; Rodniin [2], DkTx [3], and Hi1a [4] which appear to have formed via domain duplication, resulting in the emergence of peptide bivalency. In the tandem repeat peptides, i.e. SCREPs, researchers have found a gain in avidity, a property lacking in the single domain counterparts. ScrepYard supports the daunting task of engineering bivalent ligands by providing a natural source of evolutionary refined multivalent peptides.
The SCREPs database was originally generated to satisfy our own curiosity, allowing us to explore if this gain in avidity through domain duplication was a general property evolved in other DRPs. Our initial exploration of SCREPs have proven this to be the case (unpublished results) and our long-term goal is to better characterise SCREPs to determine how domain fusion (via specific linker sequences) results in the observed avidity of these fascinating molecules – with the hope of one day engineering this trait into known single domain peptides. This is a vision and undertaking that is beyond a single research team and we hope that ScrepYard [5], and its many tools, will provide a platform for others to help realise our rather lofty vision.
About Us
ScrepYard was developed as part of an Australian Discovery Project (DP190101177) awarded to Profs Mehdi Mobli (Centre for Advanced Imaging [CAI], UQ) and A/Profs Eivind Undheim (UQ Centre for Advanced Imaging; NTNU Department of Biology, Norway; and University of Oslo Department of Biosciences, also Norway). MM is a structural biologist interested in understanding the structure, function and mechanism-of-action of disulfide-rich peptides and their receptors. EU is a biologist interested in the molecular processes that drive the evolution of traits and how these processes affect each other across levels of biological complexity.
The two researchers lead the SCREPs team where Dr Michael Maxwell is involved in both the population and curation of ScrepYard as well as the characterisation of bioactive SCREPs identified through ScrepYard. Junyu Liu is reading a PhD involving both the optimisation and automation of the curation process developed by himself and Michael Maxwell as well as the characterization of bioactive SCREPs identified through this resource.
While the team are capable tinkerers of code and bioinformatics, the realisation of ScrepYard as a functioning online resource has only been made possible in its sleek design through the efforts of Thom Cuddihy, Madeline Bassetti, and Cameron Hyde from QFAB and QCIF.
Finally, we owe thanks to our talented friend Shervin Sheikhan for spending his valuable time developing a logo for us and cheering us up with his alternative ideas.
