Computational studies of the binding profile of phosphoinositide PtdIns (3,4,5) P₃ with the pleckstrin homology domain of an oomycete cellulose synthase.

Guanglin Kuang,Yaoquan Tu,Vincent Bulone

doi:10.1038/srep20555

Guanglin Kuang, Yaoquan Tu + Show 1 more

Open Access

https://doi.org/10.1038/srep20555

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Journal: Scientific Reports	Publication Date: Feb 9, 2016
Citations: 7	License type: CC BY 4.0

Affiliation: KTH Royal Institute of Technology, AlbaNova

Abstract

Saprolegnia monoica is a model organism to investigate Saprolegnia parasitica, an important oomycete which causes considerable loss in aquaculture every year. S. monoica contains cellulose synthases vital for oomycete growth. However, the molecular mechanism of the cellulose biosynthesis process in the oomycete growth is still poorly understood. Some cellulose synthases of S. monoica, such as SmCesA2, are found to contain a plecsktrin homology (PH) domain, which is a protein module widely found in nature and known to bind to phosphoinositides, a class of signaling compounds involved in many biological processes. Understanding the molecular interactions between the PH domain and phosphoinositides would help to unravel the cellulose biosynthesis process of oomycetes. In this work, the binding profile of PtdIns (3,4,5) P3, a typical phosphoinositide, with SmCesA2-PH was studied by molecular docking, molecular dynamics and metadynamics simulations. PtdIns (3,4,5) P3 is found to bind at a specific site located at β1, β2 and β1-β2 loop of SmCesA2-PH. The high affinity of PtdIns (3,4,5) P3 to SmCesA2-PH is contributed by the free phosphate groups, which have electrostatic and hydrogen-bond interactions with Lys88, Lys100 and Arg102 in the binding site.

Highlights

Saprolegnia monoica is a model organism to investigate Saprolegnia parasitica, an important oomycete which causes considerable loss in aquaculture every year
The plecsktrin homology (PH) domain of the human TAPP1 (TAPP1-PH) was selected as the template for homology modeling because it has the highest sequence identity (28%) with that of SmCesA2 (SmCesA2-PH)
These two loops are least conserved in this class of protein domains and are usually called variable loop 1 (VL1) and variable loop 2 (VL2) since their sequences and structures are most variable8

Summary

Introduction

Saprolegnia monoica is a model organism to investigate Saprolegnia parasitica, an important oomycete which causes considerable loss in aquaculture every year. Some cellulose synthases of S. monoica, such as SmCesA2, are found to contain a plecsktrin homology (PH) domain, which is a protein module widely found in nature and known to bind to phosphoinositides, a class of signaling compounds involved in many biological processes. In 2009, the sequences of several cellulose synthases of Saprolegnia monoica, which is closely related to S. parasitica, were determined by Fugelstad et al.. In 2009, the sequences of several cellulose synthases of Saprolegnia monoica, which is closely related to S. parasitica, were determined by Fugelstad et al.4 These findings paved the way to investigate the structural basis of Saprolegniosis and to develop anti-Saprolegniosis drugs. The binding mode of the soluble inositol head groups of PtdIns [3,4,5] P3 with SmCesA2-PH was obtained by molecular docking, molecular dynamics and metadynamics simulations. The detailed interactions between SmCesA2-PH and PtdIns [3,4,5] P3/POPC were analyzed

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