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Title: Computational Analysis of the Ligand Binding Site of the Extracellular ATP Receptor, DORN1

Abstract

DORN1 (also known as P2K1) is a plant receptor for extracellular ATP, which belongs to a large gene family of legume-type (L-type) lectin receptor kinases. Extracellular ATP binds to DORN1 with strong affinity through its lectin domain, and the binding triggers a variety of intracellular activities in response to biotic and abiotic stresses. However, information on the tertiary structure of the ligand binding site of DORN1is lacking, which hampers efforts to fully elucidate the mechanism of receptor action. Available data of the crystal structures from more than 50 L-type lectins enable us to perform an in silico study of molecular interaction between DORN1 and ATP. In this study, we employed a computational approach to develop a tertiary structure model of the DORN1 lectin domain. A blind docking analysis demonstrated that ATP binds to a cavity made by four loops (defined as loops A B, C and D) of the DORN1 lectin domain with high affinity. In silico target docking of ATP to the DORN1 binding site predicted interaction with 12 residues, located on the four loops, via hydrogen bonds and hydrophobic interactions. The ATP binding pocket is structurally similar in location to the carbohydrate binding pocket of the canonical L-typemore » lectins. However, four of the residues predicted to interact with ATP are not conserved between DORN1 and the other carbohydrate-binding lectins, suggesting that diversifying selection acting on these key residues may have led to the ATP binding activity of DORN1. Finally, the in silico model was validated by in vitro ATP binding assays using the purified extracellular lectin domain of wild-type DORN1, as well as mutated DORN1 lacking key ATP binding residues.« less

Authors:
ORCiD logo [1]; ORCiD logo [2];  [1];  [1];  [3];  [1]
  1. Univ. of Missouri, Columbia, MO (United States). Division of Plant Sciences and Biochemistry, Christopher S. Bond Life Sciences Center
  2. Washington State Univ., Pullman, WA (United States). Dept. of Plant Pathology
  3. Univ. of Missouri, Columbia, MO (United States). Dept. of Computer Science, Informatics Inst.
Publication Date:
Research Org.:
Univ. of Missouri, Columbia, MO (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); National Institutes of Health (NIH); Rural Development Administration, Republic of Korea
OSTI Identifier:
1346609
Alternate Identifier(s):
OSTI ID: 1393423
Grant/Contract Number:  
FG02-08ER15309; FG02-02ER15309
Resource Type:
Journal Article: Published Article
Journal Name:
PLoS ONE
Additional Journal Information:
Journal Volume: 11; Journal Issue: 9; Journal ID: ISSN 1932-6203
Publisher:
Public Library of Science
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; Lectins; Sequence alignment; Crystal Structure; Multiple alignment calculation; sequence databases; carbohydrates; binding analysis; sequence similarity searching

Citation Formats

Nguyen, Cuong The, Tanaka, Kiwamu, Cao, Yangrong, Cho, Sung-Hwan, Xu, Dong, and Stacey, Gary. Computational Analysis of the Ligand Binding Site of the Extracellular ATP Receptor, DORN1. United States: N. p., 2016. Web. doi:10.1371/journal.pone.0161894.
Nguyen, Cuong The, Tanaka, Kiwamu, Cao, Yangrong, Cho, Sung-Hwan, Xu, Dong, & Stacey, Gary. Computational Analysis of the Ligand Binding Site of the Extracellular ATP Receptor, DORN1. United States. doi:10.1371/journal.pone.0161894.
Nguyen, Cuong The, Tanaka, Kiwamu, Cao, Yangrong, Cho, Sung-Hwan, Xu, Dong, and Stacey, Gary. Thu . "Computational Analysis of the Ligand Binding Site of the Extracellular ATP Receptor, DORN1". United States. doi:10.1371/journal.pone.0161894.
@article{osti_1346609,
title = {Computational Analysis of the Ligand Binding Site of the Extracellular ATP Receptor, DORN1},
author = {Nguyen, Cuong The and Tanaka, Kiwamu and Cao, Yangrong and Cho, Sung-Hwan and Xu, Dong and Stacey, Gary},
abstractNote = {DORN1 (also known as P2K1) is a plant receptor for extracellular ATP, which belongs to a large gene family of legume-type (L-type) lectin receptor kinases. Extracellular ATP binds to DORN1 with strong affinity through its lectin domain, and the binding triggers a variety of intracellular activities in response to biotic and abiotic stresses. However, information on the tertiary structure of the ligand binding site of DORN1is lacking, which hampers efforts to fully elucidate the mechanism of receptor action. Available data of the crystal structures from more than 50 L-type lectins enable us to perform an in silico study of molecular interaction between DORN1 and ATP. In this study, we employed a computational approach to develop a tertiary structure model of the DORN1 lectin domain. A blind docking analysis demonstrated that ATP binds to a cavity made by four loops (defined as loops A B, C and D) of the DORN1 lectin domain with high affinity. In silico target docking of ATP to the DORN1 binding site predicted interaction with 12 residues, located on the four loops, via hydrogen bonds and hydrophobic interactions. The ATP binding pocket is structurally similar in location to the carbohydrate binding pocket of the canonical L-type lectins. However, four of the residues predicted to interact with ATP are not conserved between DORN1 and the other carbohydrate-binding lectins, suggesting that diversifying selection acting on these key residues may have led to the ATP binding activity of DORN1. Finally, the in silico model was validated by in vitro ATP binding assays using the purified extracellular lectin domain of wild-type DORN1, as well as mutated DORN1 lacking key ATP binding residues.},
doi = {10.1371/journal.pone.0161894},
journal = {PLoS ONE},
issn = {1932-6203},
number = 9,
volume = 11,
place = {United States},
year = {2016},
month = {9}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record at 10.1371/journal.pone.0161894

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Cited by: 2 works
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Works referenced in this record:

Scalable molecular dynamics with NAMD
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