9gf2

From Proteopedia

This peptide is a variant of the de novo hexameric peptide, CC-Hex2, which consists of 4 heptad repeats. This peptide has been denoted CC-Hex2 as its second heptad repeat has been replaced with a hendecad repeat.

Structural highlights

9gf2 is a 6 chain structure with sequence from Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.099Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

De novo protein design is delivering new peptide and protein structures at a rapid pace. Many of these synthetic polypeptides form well-defined and hyperthermal-stable structures. Generally, however, less is known about the dynamic properties of the de novo designed structures. Here, we explore one aspect of dynamics in a series of de novo coiled-coil peptide assemblies: namely, peptide exchange within and between different oligomers from dimers through to heptamers. First, we develop a fluorescence-based reporter assay for peptide exchange that is straightforward to implement, and, thus, would be useful to others examining similar systems. We apply this assay to explore both homotypic exchange within single species, and heterotypic exchange between coiled coils of different oligomeric states. For the former, we provide a detailed study for a dimeric coiled coil, CC-Di, finding a half-life for exchange of 4.2 +/- 0.3 minutes at a peptide concentration of 200 muM. Interestingly, more broadly when assessing exchange across all of the oligomeric states, we find that some of the designs are faithful and only undergo homotypic strand exchange, whereas others are promiscuous and exchange to form unexpected hetero-oligomers. Finally, we develop two design strategies to improve the orthogonality of the different oligomers: (i) using alternate positioning of salt bridge interactions; and (ii) incorporating non-canonical repeats into the designed sequences. In so doing, we reconcile the promiscuity and deliver a set of faithful homo-oligomeric de novo coiled-coil peptides. Our findings have implications for the application of these and other coiled coils as modules in chemical and synthetic biology.

Exchange, promiscuity, and orthogonality in de novo designed coiled-coil peptide assemblies.,Kurgan KW, Martin FJO, Dawson WM, Brunnock T, Orr-Ewing AJ, Woolfson DN Chem Sci. 2024 Dec 9. doi: 10.1039/d4sc06329e. PMID:39720134^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kurgan KW, Martin FJO, Dawson WM, Brunnock T, Orr-Ewing AJ, Woolfson DN. Exchange, promiscuity, and orthogonality in de novo designed coiled-coil peptide assemblies. Chem Sci. 2024 Dec 9. PMID:39720134 doi:10.1039/d4sc06329e