Insights from molecular modeling and dynamics simulation of pathogen resistance (R) protein from brinjal

Dipty Shrivastava,Priyanka Sharma,Prakash Chand Sharma,Polumetla Ananda Kumar,Anju Verma,Shakti Sahi,Vikrant Nain

doi:10.6026/97320630005326

Abstract

Resistance (R) protein recognizes molecular signature of pathogen infection and activates downstream hypersensitive response signalling in plants. R protein works as a molecular switch for pathogen defence signalling and represent one of the largest plant gene family. Hence, understanding molecular structure and function of R proteins has been of paramount importance for plant biologists. The present study is aimed at predicting structure of R proteins signalling domains (CC-NBS) by creating a homology model, refining and optimising the model by molecular dynamics simulation and comparing ADP and ATP binding. Based on sequence similarity with proteins of known structures, CC-NBS domains were initially modelled using CED- 4 (cell death abnormality protein) and APAF-1 (apoptotic protease activating factor) as multiple templates. The final CC-NBS structural model was built and optimized by molecular dynamic simulation for 5 nanoseconds (ns). Docking of ADP and ATP at active site shows that both ligand bind specifically with same residues and with minor difference (1 Kcal/mol) in binding energy. Sharing of binding site by ADP and ATP and low difference in their binding site makes CC-NBS suitable for working as molecular switch. Furthermore, structural superimposition elucidate that CC-NBS and CARD (caspase recruitment domains) domain of CED-4 have low RMSD value of 0.9 A° Availability of 3D structural model for both CC and NBS domains will . help in getting deeper insight in these pathogen defence genes.

Highlights

Plants are constantly attacked throughout their life cycle by a range of phytopathogens that includes viruses, mycoplasma, bacteria, fungi, nematodes, protozoa and other parasites
In the first line of defence, presence of an invading pathogen is detected by host immune system through pathogen–associated molecular patterns (PAMPs), such as bacterial flagellin, lipopolysaccharides and fungal-oomycete cellulosebinding elicitor proteins [1]
R proteins monitor the integrity of PAMPs mediated basal immune system and any perturbation of these components by effector proteins could trigger activation of R proteins

Summary

Introduction

Plants are constantly attacked throughout their life cycle by a range of phytopathogens that includes viruses, mycoplasma, bacteria, fungi, nematodes, protozoa and other parasites. In the first line of defence, presence of an invading pathogen is detected by host immune system through pathogen–associated molecular patterns (PAMPs), such as bacterial flagellin, lipopolysaccharides and fungal-oomycete cellulosebinding elicitor proteins [1]. In the second line of defence ‘gene for gene resistance’ gets activated which is governed by resistance (R) genes that recognize pathogen race specific effecter (Avr) proteins [4]. The R gene family is one of the largest known plants gene families that mediate elicitor recognition and activate downstream signalling response leading to disease resistance by localized cell death (hypersensitive response) [5]. R proteins monitor the integrity of PAMPs mediated basal immune system and any perturbation of these components by effector proteins could trigger activation of R proteins. Pathogen recognition elicits nucleotide-dependent conformational changes that might induce oligomerisation, thereby providing a scaffold for activation of downstream signalling components [6]

Methods

Discussion

Conclusion