What are the minimal folding seeds in proteins? Experimental and theoretical assessment of secondary structure propensities of small peptide fragments

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F24%3A00580275" target="_blank" >RIV/61388963:_____/24:00580275 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/24:10478140

Výsledek na webu

<a href="https://doi.org/10.1039/D3SC04960D" target="_blank" >https://doi.org/10.1039/D3SC04960D</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/d3sc04960d" target="_blank" >10.1039/d3sc04960d</a>

Jazyk výsledku

angličtina

Název v původním jazyce

What are the minimal folding seeds in proteins? Experimental and theoretical assessment of secondary structure propensities of small peptide fragments

Popis výsledku v původním jazyce

Certain peptide sequences, some of them as short as amino acid triplets, are significantly overpopulated in specific secondary structure motifs in folded protein structures. For example, 74% of the EAM triplet is found in alpha-helices, and only 3% occurs in the extended parts of proteins (typically beta-sheets). In contrast, other triplets (such as VIV and IYI) appear almost exclusively in extended parts (79% and 69%, respectively). In order to determine whether such preferences are structurally encoded in a particular peptide fragment or appear only at the level of a complex protein structure, NMR, VCD, and ECD experiments were carried out on selected tripeptides: EAM (denoted as pro-'alpha-helical' in proteins), KAM(alpha), ALA(alpha), DIC(alpha), EKF(alpha), IYI(pro-beta-sheet or more generally, pro-extended), and VIV(beta), and the reference alpha-helical CATWEAMEKCK undecapeptide. The experimental data were in very good agreement with extensive quantum mechanical conformational sampling. Altogether, we clearly showed that the pro-helical vs. pro-extended propensities start to emerge already at the level of tripeptides and can be fully developed at longer sequences. We postulate that certain short peptide sequences can be considered minimal “folding seeds“. Admittedly, the inherent secondary structure propensity can be overruled by the large intramolecular interaction energies within the folded and compact protein structures. Still, the correlation of experimental and computational data presented herein suggests that the secondary structure propensity should be considered as one of the key factors that may lead to understanding the underlying physico-chemical principles of protein structure and folding from the first principles.

Název v anglickém jazyce

What are the minimal folding seeds in proteins? Experimental and theoretical assessment of secondary structure propensities of small peptide fragments

Popis výsledku anglicky

Certain peptide sequences, some of them as short as amino acid triplets, are significantly overpopulated in specific secondary structure motifs in folded protein structures. For example, 74% of the EAM triplet is found in alpha-helices, and only 3% occurs in the extended parts of proteins (typically beta-sheets). In contrast, other triplets (such as VIV and IYI) appear almost exclusively in extended parts (79% and 69%, respectively). In order to determine whether such preferences are structurally encoded in a particular peptide fragment or appear only at the level of a complex protein structure, NMR, VCD, and ECD experiments were carried out on selected tripeptides: EAM (denoted as pro-'alpha-helical' in proteins), KAM(alpha), ALA(alpha), DIC(alpha), EKF(alpha), IYI(pro-beta-sheet or more generally, pro-extended), and VIV(beta), and the reference alpha-helical CATWEAMEKCK undecapeptide. The experimental data were in very good agreement with extensive quantum mechanical conformational sampling. Altogether, we clearly showed that the pro-helical vs. pro-extended propensities start to emerge already at the level of tripeptides and can be fully developed at longer sequences. We postulate that certain short peptide sequences can be considered minimal “folding seeds“. Admittedly, the inherent secondary structure propensity can be overruled by the large intramolecular interaction energies within the folded and compact protein structures. Still, the correlation of experimental and computational data presented herein suggests that the secondary structure propensity should be considered as one of the key factors that may lead to understanding the underlying physico-chemical principles of protein structure and folding from the first principles.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Chemical Science

ISSN

2041-6520

e-ISSN

2041-6539

Svazek periodika

15

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

15

Strana od-do

594-608

Kód UT WoS článku

001119543500001

EID výsledku v databázi Scopus

2-s2.0-85179778467