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Modeling of PH Domains and Phosphoinositides Interactions and Beyond

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Protein Reviews – Purinergic Receptors

Part of the book series: Advances in Experimental Medicine and Biology ((PROTRE,volume 1111))

Abstract

Pleckstrin homology (PH) domains form a large family of protein modules within membrane-targeting domains. PH domains can function as lipid-binding modules, and in particular bind with different specificities and affinities to phosphoinositides (PIs). Understanding the association of PH domains to PIs is critical for many aspects of cellular biology. Bioinformatics and computational modeling approaches have become standard tools to study the structure and dynamics of PH domains and PIs. In this review, recent advances in the binding specificity of PH domains and their interactions with PIs, using bioinformatics tools for the prediction of PIs binding sites, performing molecular dynamics simulations to study PH domains-PIs interactions, as well as the computational inhibitor design for PH domains guided signaling pathways have been discussed.

Jiarong Feng, Lei He and Yuqian Li contributed equally to this work.

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Abbreviations

PtdIns(4)P:

Phosphatidylinositol 4-phosphate

PtdIns(3,4)P2 :

Phosphatidylinositol 3,4-bisphosphate

PtdIns(3,5)P2 :

Phosphatidylinositol 3,5-bisphosphate

PtdIns(4,5)P2 :

Phosphatidylinositol 4,5-bisphosphate

PtdIns (3,4,5)P3 :

Phosphatidylinositol 3,4,5-triphosphate;

PtdIns(1,3,4,5)P4 :

Phosphatidylinositol 1,3,4,5-trisphosphate

Ins (4, 5)P2 :

Inositol 4,5-bisphosphate

Ins(1,4,5)P 3 :

Inositol 1,4,5-trisphosphate

Ins(1,3,4,5)P4 :

Inositol 1,3,4,5-tetrakisphosphate

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (61401068), the China Postdoctoral Science Foundation (2016 M590495), Jiangsu College Natural Science Research Key Program (17KJA520004), and the Jiangsu Planned Projects for Postdoctoral Research Funds (1601168C).

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    Authors and Affiliations

    1. School of Biology and Basic Medical Sciences, Medical College, Soochow University, Suzhou, China

      Jiarong Feng & Fei Xiao

    2. School of Radiation Medicine and Protection, Soochow University, Suzhou, China

      Lei He

    3. Cambridge-Suda (Cam-SU) Genomic Resource Center, Soochow University, Suzhou, China

      Lei He

    4. School of Electronic Engineering, University of Electronic Science and Technology of China, Chengdu, China

      Yuqian Li

    5. Center for Systems Biology, Soochow University, Suzhou, China

      Guang Hu

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    Correspondence to Fei Xiao or Guang Hu .

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    1. Biochem and Mol Biol, Baylor College of Medicine, Houston, TX, USA

      M. Zouhair Atassi

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    Feng, J., He, L., Li, Y., Xiao, F., Hu, G. (2018). Modeling of PH Domains and Phosphoinositides Interactions and Beyond. In: Atassi, M. (eds) Protein Reviews – Purinergic Receptors. Advances in Experimental Medicine and Biology(), vol 1111. Springer, Cham. https://doi.org/10.1007/5584_2018_236

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