ArticlePloS one2026
Co-evolution of RcsD and RcsF shapes signal transduction in the enterobacteriaceae Rcs system.
Article in PloS one, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Two-component systems (TCS) formed of sensor histidine kinases (HK) and response regulators (RR) are the primary prokaryotic signal transduction pathways. In Enterobacteriaceae, some TCS evolved architectural complexity, by integrating auxiliary proteins into the HK- RR dyad. The Regulator of Capsule Synthesis (Rcs), a conserved phosphorelay system in Enterobacteriaceae, recruits several auxiliary proteins, including an outer membrane lipoprotein, RcsF, which senses cell envelope threats and transduces the signal to downstream components. A second auxiliary protein located in the inner membrane, RcsD, transfers the phosphoryl group from the hybrid histidine kinase RcsC to the response regulator RcsB. RcsD is formed of a large periplasmic domain (Asn43-Asn308) sandwiched between two transmembrane helices and a cytosolic domain. For RcsD, the role and evolutionary benefit of maintaining a large periplasmic domain while the main phosphostransfer reaction occurs in the cytosol is not clear. Here, we show that RcsF and RcsD exhibit strong co-evolutionary coupling independent of host speciation (partial Mantel r = 0.950, p < 0.0001). Structure-guided docking and 500-ns molecular dynamics simulations predicted a stable interaction between RcsF and RcsD (MM-GBSA ΔG ≈ -95 kcal/mol), suggesting their functional coupling. Functional assays in Escherichia coli K12 MG1655 revealed that RcsD periplasmic domain represses basal Rcs activity in unstressed cells (~5-fold derepression) yet is essential for stress-induced activation (1.9-2.5-fold). Overexpression of rcsF beyond the chromosomal level induces Rcs signal activation only when the RcsD periplasmic domain is present. These findings demonstrate how co-evolution of an auxiliary protein generates novel regulatory function in the Rcs phosphorelay and provide insights into the role of RcsD periplasmic domain in stress signal transduction.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.