Origin of the Phosphoprotein Phosphatase (PPP) sequence family in Bacteria: Critical ancestral sequence changes, radiation patterns and substrate binding features

Kerk, David; Valdés‐Tresanco, Mario E.; Toth, Ryan; Noskov, Sergei Y.; Ng, Kenneth; Moorhead, Greg B. G.

doi:10.1016/j.bbadva.2021.100005

Cited by 3 publications

(16 citation statements)

References 82 publications

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“…As noted previously (see Supplemental Figure S3 ) the second Arg residue of the “2-Arginine Clamp” implicated in enzymatic activity in bacterial PPPs (down arrow) is also observed in all the “BacterialPPP-Like” archaeal sequences. As also noted previously 4 (see also Supplemental Figure S1 ), this residue is replaced by a structurally conserved Asp in eukaryotic PPPs (for example, Asp 208 in human PP1α). In this alignment it can be seen that this Asp is also conserved in all the “EukaryoticPPP-Like” archaeal and bacterial sequences.…”

Section: Resultssupporting

confidence: 71%

“…In this alignment it can be seen that this Asp is also conserved in all the “EukaryoticPPP-Like” archaeal and bacterial sequences. Inspection also reveals that the predicted loop in Domain 3 (dashed underline) previously noted 4 (see also Supplemental Figure S1 ) within eukaryotic PPPs is observed here in all the “EukaryoticPPP-Like” sequences (archaeal and bacterial) but not in the “BacterialPPP-Like” archaeal sequences. Near the end of this loop is an Arg residue (Arg 221 in human PP1α) (up arrow), which was previously noted 4 as the second residue of the “2-Arginine Clamp” important in phospho-substrate binding.…”

Section: Resultssupporting

confidence: 57%

“…Previous reports 4 , 5 described the evolution of bacterial PPPs from ancestral nuclease-like members of the MPE (metallophosphoesterase) superfamily 4 . We also described the important functional architecture of both bacterial and eukaryotic PPPs, including the presence of a “2-Arginine Clamp” in each sequence type which is important in phospho-substrate binding.…”

Section: Resultsmentioning

confidence: 99%

“…It is also well established that protein phosphorylation is a common regulatory mechanism in all other Eukaryotes, bacteria and archaea. In a previous study 4 we established that enzymes related to the major serine/threonine protein phosphatase family of Eukaryotes (the phospho-protein phosphatase or PPP family) is widely spread in bacteria and belongs to the broader metallophosphoesterase (MPE) (also called metallophosphatase (MPP)) superfamily. Using phylogenetics and molecular dynamics simulations we traced a likely evolutionary route from nuclease-like phosphodiesterase to a monoesterase with phospho-protein specificity in bacterial PPP enzymes 4 .…”

Section: Introductionmentioning

confidence: 99%

“…Utilizing this 4 as a framework, we have now re-examined PPP evolutionary history. Combining HMM-derived archaeal and bacterial sequence datasets within structure-guided alignments, followed by phylogenetic tree inference, we trace the origin of eukaryotic PPPs to an archaeal ancestor related to the current Asgard superphylum.…”

Section: Introductionmentioning

confidence: 99%

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The origin and radiation of the phosphoprotein phosphatase (PPP) enzymes of Eukaryotes

Kerk

Mattice

Valdés‐Tresanco

et al. 2021

Sci Rep

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Phosphoprotein phosphatase (PPP) enzymes are ubiquitous proteins involved in cellular signaling pathways and other functions. Here we have traced the origin of the PPP sequences of Eukaryotes and their radiation. Using a bacterial PPP Hidden Markov Model (HMM) we uncovered “BacterialPPP-Like” sequences in Archaea. A HMM derived from eukaryotic PPP enzymes revealed additional, unique sequences in Archaea and Bacteria that were more like the eukaryotic PPP enzymes then the bacterial PPPs. These sequences formed the basis of phylogenetic tree inference and sequence structural analysis allowing the history of these sequence types to be elucidated. Our phylogenetic tree data strongly suggest that eukaryotic PPPs ultimately arose from ancestors in the Asgard archaea. We have clarified the radiation of PPPs within Eukaryotes, substantially expanding the range of known organisms with PPP subtypes (Bsu1, PP7, PPEF/RdgC) previously thought to have a more restricted distribution. Surprisingly, sequences from the Methanosarcinaceae (Euryarchaeota) form a strongly supported sister group to eukaryotic PPPs in our phylogenetic analysis. This strongly suggests an intimate association between an Asgard ancestor and that of the Methanosarcinaceae. This is highly reminiscent of the syntrophic association recently demonstrated between the cultured Lokiarchaeal species Prometheoarchaeum and a methanogenic bacterial species.

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Section: Resultssupporting

confidence: 71%

Section: Resultssupporting

confidence: 57%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The origin and radiation of the phosphoprotein phosphatase (PPP) enzymes of Eukaryotes

Kerk

Mattice

Valdés‐Tresanco

et al. 2021

Sci Rep

Self Cite

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Mechanistic and evolutionary insights into alkaline phosphatase superfamily through structure-function studies on Sphingomonas alkaline phosphatase

Bihani

Nagar

Kumar

2023

Archives of Biochemistry and Biophysics

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Eukaryotic-like phosphoprotein phosphatase (PPP) enzyme evolution: interactions with environmental toxins and regulatory proteins

et al. 2023

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Phosphoprotein phosphatases (PPPs) are a ubiquitous class of enzymes which dephosphorylate serine and threonine residues on substrate proteins involved in a wide variety of cellular processes. The active site of PPP enzymes are highly conserved with key residues coordinating the substrate phosphoryl group (the two R-clamp) and two metal ions necessary for catalysis. Because of the diverse number of roles that these enzymes play it is no surprise that they are highly regulated in the cell, often accomplished by binding regulatory subunits. These regulatory subunits are able to dictate substrate specificity, localization, and activity of the bound catalytic subunit. Eukaryotic PPP subtypes have been previously shown to manifest varying degrees of sensitivity to environmental toxins. We present here an evolutionary model which now rationalizes this data. Our re-examination of published structural evidence reveals that Eukaryotic PPP toxin-binding residues also interact with substrate binding residues (the two R-clamp) and ancient regulatory proteins. Such functional interactions could have stabilized PPP sequence early in Eukaryotic evolution, providing a stable target which was co-opted by toxins and their producer organisms.

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Origin of the Phosphoprotein Phosphatase (PPP) sequence family in Bacteria: Critical ancestral sequence changes, radiation patterns and substrate binding features

Cited by 3 publications

References 82 publications

The origin and radiation of the phosphoprotein phosphatase (PPP) enzymes of Eukaryotes

The origin and radiation of the phosphoprotein phosphatase (PPP) enzymes of Eukaryotes

Mechanistic and evolutionary insights into alkaline phosphatase superfamily through structure-function studies on Sphingomonas alkaline phosphatase

Eukaryotic-like phosphoprotein phosphatase (PPP) enzyme evolution: interactions with environmental toxins and regulatory proteins

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