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Proteome-scale relationships between local amino acid composition and protein fates and functions.

ABSTRACT: Proteins with low-complexity domains continue to emerge as key players in both normal and pathological cellular processes. Although low-complexity domains are often grouped into a single class, individual low-complexity domains can differ substantially with respect to amino acid composition. These differences may strongly influence the physical properties, cellular regulation, and molecular functions of low-complexity domains. Therefore, we developed a bioinformatic approach to explore relationships between amino acid composition, protein metabolism, and protein function. We find that local compositional enrichment within protein sequences is associated with differences in translation efficiency, abundance, half-life, protein-protein interaction promiscuity, subcellular localization, and molecular functions of proteins on a proteome-wide scale. However, local enrichment of related amino acids is sometimes associated with opposite effects on protein regulation and function, highlighting the importance of distinguishing between different types of low-complexity domains. Furthermore, many of these effects are discernible at amino acid compositions below those required for classification as low-complexity or statistically-biased by traditional methods and in the absence of homopolymeric amino acid repeats, indicating that thresholds employed by classical methods may not reflect biologically relevant criteria. Application of our analyses to composition-driven processes, such as the formation of membraneless organelles, reveals distinct composition profiles even for closely related organelles. Collectively, these results provide a unique perspective and detailed insights into relationships between amino acid composition, protein metabolism, and protein functions.

SUBMITTER: Cascarina SM

PROVIDER: S-EPMC6171957 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Proteome-scale relationships between local amino acid composition and protein fates and functions.

Cascarina Sean M SM Ross Eric D ED

PLoS computational biology 20180924 9

Proteins with low-complexity domains continue to emerge as key players in both normal and pathological cellular processes. Although low-complexity domains are often grouped into a single class, individual low-complexity domains can differ substantially with respect to amino acid composition. These differences may strongly influence the physical properties, cellular regulation, and molecular functions of low-complexity domains. Therefore, we developed a bioinformatic approach to explore relations ...[more]

PMID: 30248088

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Project description:Different dietary nitrogen (N) patterns may have different effects on gut microbiota. To investigate the effects of different crude protein (CP) levels or essential amino acids (EAA) supplementation patterns on the structure and functions of colonic microbiota, 42 barrows (25 ± 0.39 kg) were randomly assigned to 7 dietary treatments including: diet 1, a high CP diet with balanced 10 EAA; diet 2, a medium CP diet with approximately 2% decreased CP level from diet 1 and balanced 10 EAA; diets 3, 4, 5, 6 and 7, low CP diets with 4% decreased CP level from diet 1. Specifically, diet 3 was only balanced for Lys, Met, Thr and Trp; diets 4, 5 and 6 were further supplemented with Ile, Val and Ile + Val on the basis of diet 3, respectively; and diet 7 was balanced for 10 EAA. Results over a 110-d trial showed that reducing the CP level by 2% or 4% dramatically decreased N intake and excretion (P < 0.05) in the presence of balanced 10 EAA, which was not observed when altering the EAA supplementation patterns in low CP diet (-4%). With balanced 10 EAA, 2% reduction in dietary CP significantly reduced Firmicutes-to-Bacteroidetes (F:B) ratio and significantly elevated the abundance of Prevotellaceae NK3B31 (P < 0.05); whereas 4% reduction evidently increased the abundances of Proteobacteria, Succinivibrio and Lachnospiraceae XPB1014 (P < 0.05). Among the 5 low CP diets (-4%), supplementation with Ile, or Val + Ile, or balanced 10 EAA increased F:B ratio and the abundance of Proteobacteria. In addition, the predicted functions revealed that different CP levels and EAA balanced patterns dramatically altered the mRNA expression profiles of N-metabolizing genes, the "N and energy metabolism" pathways or the metabolism of some small substances, such as amino acids (AA) and vitamins. Our findings suggested that reducing the dietary CP levels by 2% to 4% with balancing 10 EAA, or only further supplementation with Ile or Val + Ile to a low protein diet (-4%) reduced the N contents entering the hindgut to various degrees, altered the abundances of N-metabolizing bacteria, and improved the abilities of N utilization.

Dataset Information

Proteome-scale relationships between local amino acid composition and protein fates and functions.

Publications

Proteome-scale relationships between local amino acid composition and protein fates and functions.

Similar Datasets

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