Sequential modification of bacterial chemoreceptors is key for achieving both accurate adaptation and high gain

Many regulatory and signaling proteins have multiple modification sites. In bacterial chemotaxis, each chemoreceptor has multiple methylation sites that are responsible for adaptation. However, whether the ordering of the multisite methylation process affects adaptation remains unclear. Furthermore,...

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Bibliographic Details
Published in:	Nature communications Vol. 11; no. 1; p. 2875
Main Authors:	Mello, Bernardo A., Beserra, Anderson B., Tu, Yuhai
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 08-06-2020 Nature Publishing Group Nature Portfolio
Subjects:	119/118 631/114 631/326/41/2095 631/553/2710 Accuracy Adaptation Adaptation, Physiological Bacteria Bacterial Proteins - metabolism Chemoreceptor Cells - metabolism Chemoreceptors Chemotaxis Demethylation High gain Humanities and Social Sciences Methylation Models, Biological multidisciplinary Science Science (multidisciplinary) Tradeoffs
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Summary:	Many regulatory and signaling proteins have multiple modification sites. In bacterial chemotaxis, each chemoreceptor has multiple methylation sites that are responsible for adaptation. However, whether the ordering of the multisite methylation process affects adaptation remains unclear. Furthermore, the benefit of having multiple modification sites is also unclear. Here, we show that sequentially ordered methylation/demethylation is critical for perfect adaptation; adaptation accuracy decreases as randomness in the multisite methylation process increases. A tradeoff between adaptation accuracy and response gain is discovered. We find that this accuracy-gain tradeoff is lifted significantly by having more methylation sites, but only when the multisite modification process is sequential. Our study suggests that having multiple modification sites and a sequential modification process constitute a general strategy to achieve both accurate adaptation and high response gain simultaneously. Our theory agrees with existing data and predictions are made to help identify the molecular mechanism underlying ordered covalent modifications. Bacterial chemoreceptors have multiple methylation sites, but whether the order of methylation matters is unclear. Here, the authors show that sequentially ordered methylation is critical for perfect adaptation and for attenuating the trade-off between accurate adaptation and high response gain.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-020-16644-4