Frame Shifts Affect the Stability of Collagen Triple Helices

J 2022

Frame Shifts Affect the Stability of Collagen Triple Helices

FIALA, Tomáš; Emilia P BARROS; Marc-Olivier EBERT; Enrico RUIJSENAARS; Sereina RINIKER et al.

Základní údaje

Originální název

Frame Shifts Affect the Stability of Collagen Triple Helices

Autoři

FIALA, Tomáš ; Emilia P BARROS; Marc-Olivier EBERT; Enrico RUIJSENAARS; Sereina RINIKER a Helma WENNEMERS

Vydání

Journal of the American Chemical Society, WASHINGTON, AMER CHEMICAL SOC, 2022, 0002-7863

Další údaje

Typ výsledku

Článek v odborném periodiku

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 15.000

Označené pro přenos do RIV

DOI

https://doi.org/10.1021/jacs.2c08727

Štítky

ne MU, ne RIV

Změněno: 17. 2. 2025 10:31, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

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 degrees 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 degrees C apart. A combination of thermal denaturation, circular dichroism 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.

Citovat

FIALA, Tomáš; Emilia P BARROS; Marc-Olivier EBERT; Enrico RUIJSENAARS; Sereina RINIKER a Helma WENNEMERS. Frame Shifts Affect the Stability of Collagen Triple Helices. Journal of the American Chemical Society. WASHINGTON: AMER CHEMICAL SOC, 2022, 8 s. ISSN 0002-7863. Dostupné z: https://doi.org/10.1021/jacs.2c08727.

@article{2477820,
   author = {Fiala, Tomáš and Barros, Emilia P and Ebert, MarcandOlivier and Ruijsenaars, Enrico and Riniker, Sereina and Wennemers, Helma},
   article_location = {WASHINGTON},
   doi = {https://doi.org/10.1021/jacs.2c08727},
   issn = {0002-7863},
   journal = {Journal of the American Chemical Society},
   note = {nevzniklo na MU},
   title = {Frame Shifts Affect the Stability of Collagen Triple Helices},
   year = {2022}
}

TY  - JOUR
ID  - 2477820
AU  - Fiala, Tomáš - Barros, Emilia P - Ebert, Marc-Olivier - Ruijsenaars, Enrico - Riniker, Sereina - Wennemers, Helma
PY  - 2022
TI  - Frame Shifts Affect the Stability of Collagen Triple Helices
JF  - Journal of the American Chemical Society
PB  - AMER CHEMICAL SOC
SN  - 00027863
N1  - nevzniklo na MU
N2  - 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 degrees 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 degrees C apart. A combination of thermal denaturation, circular dichroism 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.
ER  -

FIALA, Tomáš; Emilia P BARROS; Marc-Olivier EBERT; Enrico RUIJSENAARS; Sereina RINIKER a Helma WENNEMERS. Frame Shifts Affect the Stability of Collagen Triple Helices. \textit{Journal of the American Chemical Society}. WASHINGTON: AMER CHEMICAL SOC, 2022, 8 s. ISSN~0002-7863. Dostupné z: https://doi.org/10.1021/jacs.2c08727.

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