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Positively-charged semi-tunnel is a structural and surface characteristic of polyphosphate-binding proteins: an in-silico study.

Wei ZZ, Vatcher G, Tin AH, Teng JL, Wang J, Cui QH, Chen JG, Yu AC - PLoS ONE (2015)

Bottom Line: We found that the PCSTs in varied proteins were folded in different secondary structure compositions.Utilizing the PCST identified in the β subunit of PPK3, we predicted the potential polyP-binding domain of PPK3.The discovery of this feature facilitates future searches for polyP-binding proteins and discovery of the mechanisms for polyP-binding activities.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Research Institute, Peking University; Department of Neurobiology, School of Basic Medical Sciences, Peking University; Key Laboratory for Neuroscience (Peking University), Ministry of Education; Key Laboratory for Neuroscience (Peking University), National Health and Family Planning Commission, Beijing 100191, China.

ABSTRACT
Phosphate is essential for all major life processes, especially energy metabolism and signal transduction. A linear phosphate polymer, polyphosphate (polyP), linked by high-energy phosphoanhydride bonds, can interact with various proteins, playing important roles as an energy source and regulatory factor. However, polyP-binding structures are largely unknown. Here we proposed a putative polyP binding site, a positively-charged semi-tunnel (PCST), identified by surface electrostatics analyses in polyP kinases (PPKs) and many other polyP-related proteins. We found that the PCSTs in varied proteins were folded in different secondary structure compositions. Molecular docking calculations revealed a significant value for binding affinity to polyP in PCST-containing proteins. Utilizing the PCST identified in the β subunit of PPK3, we predicted the potential polyP-binding domain of PPK3. The discovery of this feature facilitates future searches for polyP-binding proteins and discovery of the mechanisms for polyP-binding activities. This should greatly enhance the understanding of the many physiological functions of protein-bound polyP and the involvement of polyP and polyP-binding proteins in various human diseases.

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Model structures of Positively-Charged Semi-Tunnel (PCST).(A) PPK4 (PDB ID: 3G3Q); (B) PPK1 (PDB ID: 1XDP); (C) PPX/GPPA (PDB ID: 1T6C); (D) HsPLAP (PDB ID: 1EW2). Protein structure (left) and protein surface graphic (right). Colors on graphics represent surface charges of the 3D structure of the protein. Blue = positive; Red = negative. Yellow double end arrows indicate observed strip of PCST.
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pone.0123713.g001: Model structures of Positively-Charged Semi-Tunnel (PCST).(A) PPK4 (PDB ID: 3G3Q); (B) PPK1 (PDB ID: 1XDP); (C) PPX/GPPA (PDB ID: 1T6C); (D) HsPLAP (PDB ID: 1EW2). Protein structure (left) and protein surface graphic (right). Colors on graphics represent surface charges of the 3D structure of the protein. Blue = positive; Red = negative. Yellow double end arrows indicate observed strip of PCST.

Mentions: By surface electrostatics analyses, we observed the positively-charged area within the surfaces of many other polyP-related proteins (both enzymes and regulatory proteins) where positively-charged amino acid residues constituted a tunnel or semi-tunnel structure. We defined this structure as a “positively-charged semi-tunnel” and potentially identified other proteins that contained PCSTs (S1 Table with their sequence and functional characteristics). We noticed that the PCST was long enough for at least four linearly-linked phosphate groups and that the inside diameter was able to accommodate the phosphate group (Fig 1A).


Positively-charged semi-tunnel is a structural and surface characteristic of polyphosphate-binding proteins: an in-silico study.

Wei ZZ, Vatcher G, Tin AH, Teng JL, Wang J, Cui QH, Chen JG, Yu AC - PLoS ONE (2015)

Model structures of Positively-Charged Semi-Tunnel (PCST).(A) PPK4 (PDB ID: 3G3Q); (B) PPK1 (PDB ID: 1XDP); (C) PPX/GPPA (PDB ID: 1T6C); (D) HsPLAP (PDB ID: 1EW2). Protein structure (left) and protein surface graphic (right). Colors on graphics represent surface charges of the 3D structure of the protein. Blue = positive; Red = negative. Yellow double end arrows indicate observed strip of PCST.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4400040&req=5

pone.0123713.g001: Model structures of Positively-Charged Semi-Tunnel (PCST).(A) PPK4 (PDB ID: 3G3Q); (B) PPK1 (PDB ID: 1XDP); (C) PPX/GPPA (PDB ID: 1T6C); (D) HsPLAP (PDB ID: 1EW2). Protein structure (left) and protein surface graphic (right). Colors on graphics represent surface charges of the 3D structure of the protein. Blue = positive; Red = negative. Yellow double end arrows indicate observed strip of PCST.
Mentions: By surface electrostatics analyses, we observed the positively-charged area within the surfaces of many other polyP-related proteins (both enzymes and regulatory proteins) where positively-charged amino acid residues constituted a tunnel or semi-tunnel structure. We defined this structure as a “positively-charged semi-tunnel” and potentially identified other proteins that contained PCSTs (S1 Table with their sequence and functional characteristics). We noticed that the PCST was long enough for at least four linearly-linked phosphate groups and that the inside diameter was able to accommodate the phosphate group (Fig 1A).

Bottom Line: We found that the PCSTs in varied proteins were folded in different secondary structure compositions.Utilizing the PCST identified in the β subunit of PPK3, we predicted the potential polyP-binding domain of PPK3.The discovery of this feature facilitates future searches for polyP-binding proteins and discovery of the mechanisms for polyP-binding activities.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Research Institute, Peking University; Department of Neurobiology, School of Basic Medical Sciences, Peking University; Key Laboratory for Neuroscience (Peking University), Ministry of Education; Key Laboratory for Neuroscience (Peking University), National Health and Family Planning Commission, Beijing 100191, China.

ABSTRACT
Phosphate is essential for all major life processes, especially energy metabolism and signal transduction. A linear phosphate polymer, polyphosphate (polyP), linked by high-energy phosphoanhydride bonds, can interact with various proteins, playing important roles as an energy source and regulatory factor. However, polyP-binding structures are largely unknown. Here we proposed a putative polyP binding site, a positively-charged semi-tunnel (PCST), identified by surface electrostatics analyses in polyP kinases (PPKs) and many other polyP-related proteins. We found that the PCSTs in varied proteins were folded in different secondary structure compositions. Molecular docking calculations revealed a significant value for binding affinity to polyP in PCST-containing proteins. Utilizing the PCST identified in the β subunit of PPK3, we predicted the potential polyP-binding domain of PPK3. The discovery of this feature facilitates future searches for polyP-binding proteins and discovery of the mechanisms for polyP-binding activities. This should greatly enhance the understanding of the many physiological functions of protein-bound polyP and the involvement of polyP and polyP-binding proteins in various human diseases.

Show MeSH
Related in: MedlinePlus