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Structural insights into ligand binding of PGRP1 splice variants in Chinese giant salamander (Andrias davidianus) from molecular dynamics and free energy calculations

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Abstract

Peptidoglycan (PGN) recognition proteins (PGRPs) are important pattern recognition receptors of the innate immune system. A number of PGRP splicing variants produced by alternative splicing of PGRP genes have been reported. However, several important aspects of interactions between PGRP splice variants and their ligands are still unclear. In the present study, three dimensional models of salamander PGRP1 (adPGRP1) and its splice variant (adPGRP1a) were constructed, and their key amino acids involved in interacting with PGNs were analyzed. The results revealed that adPGRP1a has a typical PGRPs structure containing five β-sheets and four α-helices, while adPGRP1 contained five β-sheets and only one α-helix due to the lack of 51 amino acids at its C-terminus. Molecular docking revealed that van der Waals and Coulombic interactions contributed to interactions in the protein–ligand complex. Further binding energy of adPGRP-PGNs computed by the MM-PBSA method revealed that adPGRP1a and adPGRP1 might selectively bind to different PGNs; the former might selectively bind Dap-type PGNs and the latter both types of PGNs. In addition, the binding energy of each residue of adPGRP1a and adPGRP1 was also calculated, revealing that residues involved in the interaction of protein–ligand complexes were different in adPGRP1a and adPGRP1. These results provided a first insight into the potential basis for interaction between PGRPs generated by alternative splicing and PGN derivatives.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant no. 31302221, 31272666 and 31470130) and Jiangsu Province (Grant no. BK2011418 and BK20151297), and partially by the Major Projects of Natural Science Research in Universities and Colleges in Jiangsu Province (Grant no. 15KJA240001). Z.Q. was financially supported by the “Qinglan” project of Jiangsu province of China.

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Authors and Affiliations

  1. Jiangsu Key Laboratory of Biochemistry and Biotechnology of Marine Wetland, Yancheng Institute of Technology, Yancheng, 224051, Jiangsu, China

    Zhitao Qi, Qihuan Zhang, Wei Xu & Rong Shao

  2. Key Laboratory of Aquaculture and Ecology of Coastal Pool in Jiangsu Province, Yancheng Institute of Technology, Yancheng, 224051, Jiangsu, China

    Zhitao Qi, Zisheng Wang & Guo Qiao

  3. Tianjin Institute of Pharmaceutical Research, Tianjin, 300193, China

    Fancui Meng

  4. Department of Chemistry, National Sun Yat-Sen University, Kaohsiung, 80424, Taiwan, Republic of China

    Chenglung Chen

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  1. Zhitao Qi
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Qi, Z., Meng, F., Zhang, Q. et al. Structural insights into ligand binding of PGRP1 splice variants in Chinese giant salamander (Andrias davidianus) from molecular dynamics and free energy calculations. J Mol Model 23, 135 (2017). https://doi.org/10.1007/s00894-017-3315-y

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