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Acanthamoeba castellanii STAT protein.

Kicinska A, Leluk J, Jarmuszkiewicz W - PLoS ONE (2014)

Bottom Line: A. castellanii is the only, studied to date, Amoebozoan that does not belong to Mycetozoa but possesses STATs.The A. castellanii STAT protein branches next to a group of STATc proteins from Mycetozoa.We also demonstrate that Amoebozoa form a distinct monophyletic lineage within the STAT protein world that is well separated from the other groups.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioenergetics, Adam Mickiewicz University, Poznan, Poland.

ABSTRACT
STAT (signal transducers and activators of transcription) proteins are one of the important mediators of phosphotyrosine-regulated signaling in metazoan cells. We described the presence of STAT protein in a unicellular, free-living amoebae with a simple life cycle, Acanthamoeba castellanii. A. castellanii is the only, studied to date, Amoebozoan that does not belong to Mycetozoa but possesses STATs. A sequence of the A. castellanii STAT protein includes domains similar to those of the Dictyostelium STAT proteins: a coiled coil (characteristic for Dictyostelium STAT coiled coil), a STAT DNA-binding domain and a Src-homology domain. The search for protein sequences homologous to A. castellanii STAT revealed 17 additional sequences from lower eukaryotes. Interestingly, all of these sequences come from Amoebozoa organisms that belong to either Mycetozoa (slime molds) or Centramoebida. We showed that there are four separated clades within the slime mold STAT proteins. The A. castellanii STAT protein branches next to a group of STATc proteins from Mycetozoa. We also demonstrate that Amoebozoa form a distinct monophyletic lineage within the STAT protein world that is well separated from the other groups.

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A. castellanii STAT protein domains.(A) The overview of the protein domains. The residues that form phosphotyrosine binding pocket, hydrophobic binding pocket and homodimer binding interface are indicated with arrows. (B) The SH2 domain sequence. The residues that form the phosphotyrosine binding pocket, hydrophobic binding pocket and homodimer binding interface are in red color.
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pone-0111345-g001: A. castellanii STAT protein domains.(A) The overview of the protein domains. The residues that form phosphotyrosine binding pocket, hydrophobic binding pocket and homodimer binding interface are indicated with arrows. (B) The SH2 domain sequence. The residues that form the phosphotyrosine binding pocket, hydrophobic binding pocket and homodimer binding interface are in red color.

Mentions: The predicted protein sequence of the A. castellanii STAT protein is 689 residue long, with a predicted molecular weight of 77 kDa. The similarity search revealed that this is a STAT protein that resembles the STAT proteins from slime molds. The sequence includes domains characteristic of the Dictyostelium STAT proteins (Figure 1A). The predicted protein structure (using the SUPERFAMILY database) in the region between amino acids 220 and 325 forms a coiled coil similar to that of the Dictyostelium STAT coiled coil (E-value 2.3e-18). The region between residues 332–548 is predicted to be a STAT DNA-binding domain (E-value 2.53e-06). The C-terminal fragment of the protein (amino acids 551–668) includes the Src-homology domain (SH2) found in the STAT family (E-value 6.82e-21). This SH2 domain includes polypeptide binding fragments: phosphotyrosine binding pocket (residues 566, 584, 607 and 609), hydrophobic binding pocket (residues 608 and 628) and homodimer interface (residues 622 and 623) (Figure 1B). At the C-terminus (residue 677), A. castellanii STAT possesses the conservative Y residue that is phosphorylated during STAT activation. The alignment of the A. castellanii STAT fragments with the consensus sequence for corresponding structural elements are shown in Figure 2. The N-terminal domain of the protein contains a 220-residue fragment that is unrelated in sequence to any other proteins. This domain has little predicted secondary structure and contains long runs of poly(Gln) residues that are encoded by poly(CAG) tracts. Similar to the Dictyostelium STAT proteins [32], the protein from A. castellanii does not contain a STAT protein transactivation domain or an N-terminal α-helical domain. Both of these fragments are important for mammalian STAT protein function and play a role in binding coactivators, STAT activation, deactivation, and the stabilization of interactions between STAT dimers on adjacent DNA binding sites [33].


Acanthamoeba castellanii STAT protein.

Kicinska A, Leluk J, Jarmuszkiewicz W - PLoS ONE (2014)

A. castellanii STAT protein domains.(A) The overview of the protein domains. The residues that form phosphotyrosine binding pocket, hydrophobic binding pocket and homodimer binding interface are indicated with arrows. (B) The SH2 domain sequence. The residues that form the phosphotyrosine binding pocket, hydrophobic binding pocket and homodimer binding interface are in red color.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4206453&req=5

pone-0111345-g001: A. castellanii STAT protein domains.(A) The overview of the protein domains. The residues that form phosphotyrosine binding pocket, hydrophobic binding pocket and homodimer binding interface are indicated with arrows. (B) The SH2 domain sequence. The residues that form the phosphotyrosine binding pocket, hydrophobic binding pocket and homodimer binding interface are in red color.
Mentions: The predicted protein sequence of the A. castellanii STAT protein is 689 residue long, with a predicted molecular weight of 77 kDa. The similarity search revealed that this is a STAT protein that resembles the STAT proteins from slime molds. The sequence includes domains characteristic of the Dictyostelium STAT proteins (Figure 1A). The predicted protein structure (using the SUPERFAMILY database) in the region between amino acids 220 and 325 forms a coiled coil similar to that of the Dictyostelium STAT coiled coil (E-value 2.3e-18). The region between residues 332–548 is predicted to be a STAT DNA-binding domain (E-value 2.53e-06). The C-terminal fragment of the protein (amino acids 551–668) includes the Src-homology domain (SH2) found in the STAT family (E-value 6.82e-21). This SH2 domain includes polypeptide binding fragments: phosphotyrosine binding pocket (residues 566, 584, 607 and 609), hydrophobic binding pocket (residues 608 and 628) and homodimer interface (residues 622 and 623) (Figure 1B). At the C-terminus (residue 677), A. castellanii STAT possesses the conservative Y residue that is phosphorylated during STAT activation. The alignment of the A. castellanii STAT fragments with the consensus sequence for corresponding structural elements are shown in Figure 2. The N-terminal domain of the protein contains a 220-residue fragment that is unrelated in sequence to any other proteins. This domain has little predicted secondary structure and contains long runs of poly(Gln) residues that are encoded by poly(CAG) tracts. Similar to the Dictyostelium STAT proteins [32], the protein from A. castellanii does not contain a STAT protein transactivation domain or an N-terminal α-helical domain. Both of these fragments are important for mammalian STAT protein function and play a role in binding coactivators, STAT activation, deactivation, and the stabilization of interactions between STAT dimers on adjacent DNA binding sites [33].

Bottom Line: A. castellanii is the only, studied to date, Amoebozoan that does not belong to Mycetozoa but possesses STATs.The A. castellanii STAT protein branches next to a group of STATc proteins from Mycetozoa.We also demonstrate that Amoebozoa form a distinct monophyletic lineage within the STAT protein world that is well separated from the other groups.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioenergetics, Adam Mickiewicz University, Poznan, Poland.

ABSTRACT
STAT (signal transducers and activators of transcription) proteins are one of the important mediators of phosphotyrosine-regulated signaling in metazoan cells. We described the presence of STAT protein in a unicellular, free-living amoebae with a simple life cycle, Acanthamoeba castellanii. A. castellanii is the only, studied to date, Amoebozoan that does not belong to Mycetozoa but possesses STATs. A sequence of the A. castellanii STAT protein includes domains similar to those of the Dictyostelium STAT proteins: a coiled coil (characteristic for Dictyostelium STAT coiled coil), a STAT DNA-binding domain and a Src-homology domain. The search for protein sequences homologous to A. castellanii STAT revealed 17 additional sequences from lower eukaryotes. Interestingly, all of these sequences come from Amoebozoa organisms that belong to either Mycetozoa (slime molds) or Centramoebida. We showed that there are four separated clades within the slime mold STAT proteins. The A. castellanii STAT protein branches next to a group of STATc proteins from Mycetozoa. We also demonstrate that Amoebozoa form a distinct monophyletic lineage within the STAT protein world that is well separated from the other groups.

Show MeSH