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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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Related in: MedlinePlus

PPK3 3D structure of subunits.(A) β subunit; (B) ξ subunit; (C) α subunit. 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.g006: PPK3 3D structure of subunits.(A) β subunit; (B) ξ subunit; (C) α subunit. 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: We then determined the presence of the PCST structure in PPK3. Surface electrostatics analyses showed more widespread distributions of basic residues in the α and β subunits compared to the ξ subunit (Fig 6), probably facilitating the interactions of these subunits with the phosphate of a nucleotide/polyP. Furthermore, the β subunit possessed a typical PCST structure. Combined with the docking results and the PCST structure identification in all the PPKs, our data suggested the capability of PPK3β to bind polyP. Utilization of molecular docking calculations revealed high nucleotide affinity of the three PPK3 subunits, but only the β subunit showed specific polyP affinity. Because a PCST existed in the β subunit, but not in the α or ξ subunits, our data supported the high correlation of the PCST to polyP functionality.


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)

PPK3 3D structure of subunits.(A) β subunit; (B) ξ subunit; (C) α subunit. 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.g006: PPK3 3D structure of subunits.(A) β subunit; (B) ξ subunit; (C) α subunit. 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: We then determined the presence of the PCST structure in PPK3. Surface electrostatics analyses showed more widespread distributions of basic residues in the α and β subunits compared to the ξ subunit (Fig 6), probably facilitating the interactions of these subunits with the phosphate of a nucleotide/polyP. Furthermore, the β subunit possessed a typical PCST structure. Combined with the docking results and the PCST structure identification in all the PPKs, our data suggested the capability of PPK3β to bind polyP. Utilization of molecular docking calculations revealed high nucleotide affinity of the three PPK3 subunits, but only the β subunit showed specific polyP affinity. Because a PCST existed in the β subunit, but not in the α or ξ subunits, our data supported the high correlation of the PCST to polyP functionality.

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