Frame Shifts Affect the Stability of Collagen Triple Helices
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Date
2022-10-12
Publication Type
Journal Article
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yes
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Abstract
Collagen model peptides (CMPs), composed of proline–(2S,4R)-hydroxyproline–glycine (POG) repeat units, have been extensively used to study the structure and stability of triple-helical collagen – the dominant structural protein in mammals – at the molecular level. Despite the more than 50-year history of CMPs and numerous studies on the relationship between the composition of single-stranded CMPs and the thermal stability of the assembled triple helices, little attention has been paid to the effects arising from their terminal residues. Here, we show that frame-shifted CMPs, which share POG repeat units but terminate with P, O, or G, form triple helices with vastly different thermal stabilities. A melting temperature difference as high as 16 °C was found for triple helices from 20-mers Ac-OG[POG]6-NH2 and Ac-[POG]6PO-NH2 and triple helices of the constitutional isomers Ac-[POG]7-NH2 and Ac-[GPO]7-NH2 melt 10 °C apart. A combination of thermal denaturation, CD and NMR spectroscopic studies, and molecular dynamics simulations revealed that the stability differences originate from the propensity of the peptide termini to preorganize into a polyproline-II helical structure. Our results advise that care must be taken when designing peptide mimics of structural proteins as subtle changes in the terminal residues can significantly affect their properties. Our findings also provide a general and straightforward tool for tuning the stability of CMPs for applications as synthetic materials and biological probes.
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published
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Journal / series
Volume
144 (40)
Pages / Article No.
18642 - 18649
Publisher
American Chemical Society
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Organisational unit
09458 - Riniker, Sereina Z. / Riniker, Sereina Z.
03940 - Wennemers, Helma / Wennemers, Helma
Notes
This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of the American Chemical Society, copyright © 2022 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/10.1021/jacs.2c08727
Funding
207505 - Synthetic Collagen (SNF)
891009 - Collagen Origami (EC)
891009 - Collagen Origami (EC)