Early Selection of the Amino Acid Alphabet Was Adaptively Shaped by Biophysical Constraints of Foldability

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F23%3A00569403" target="_blank" >RIV/61388963:_____/23:00569403 - isvavai.cz</a>

Alternative codes found

RIV/86652036:_____/23:00569403 RIV/00216208:11310/23:10474053

Result on the web

<a href="https://doi.org/10.1021/jacs.2c12987" target="_blank" >https://doi.org/10.1021/jacs.2c12987</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/jacs.2c12987" target="_blank" >10.1021/jacs.2c12987</a>

Result language

angličtina

Original language name

Early Selection of the Amino Acid Alphabet Was Adaptively Shaped by Biophysical Constraints of Foldability

Original language description

Whereas modern proteins rely on a quasi-universal repertoire of 20 canonical amino acids (AAs), numerous lines of evidence suggest that ancient proteins relied on a limited alphabet of 10 “early” AAs and that the 10 “late” AAs were products of biosynthetic pathways. However, many nonproteinogenic AAs were also prebiotically available, which begs two fundamental questions: Why do we have the current modern amino acid alphabet and would proteins be able to fold into globular structures as well if different amino acids comprised the genetic code? Here, we experimentally evaluate the solubility and secondary structure propensities of several prebiotically relevant amino acids in the context of synthetic combinatorial 25-mer peptide libraries. The most prebiotically abundant linear aliphatic and basic residues were incorporated along with or in place of other early amino acids to explore these alternative sequence spaces. The results show that foldability was likely a critical factor in the selection of the canonical alphabet. Unbranched aliphatic amino acids were purged from the proteinogenic alphabet despite their high prebiotic abundance because they generate polypeptides that are oversolubilized and have low packing efficiency. Surprisingly, we find that the inclusion of a short-chain basic amino acid also decreases polypeptides’ secondary structure potential, for which we suggest a biophysical model. Our results support the view that, despite lacking basic residues, the early canonical alphabet was remarkably adaptive at supporting protein folding and explain why basic residues were only incorporated at a later stage of protein evolution.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2023

Confidentiality

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

Name of the periodical

Journal of the American Chemical Society

ISSN

0002-7863

e-ISSN

1520-5126

Volume of the periodical

145

Issue of the periodical within the volume

9

Country of publishing house

US - UNITED STATES

Number of pages

10

Pages from-to

5320-5329

UT code for WoS article

000938213200001

EID of the result in the Scopus database

2-s2.0-85148939989