In:
PLOS Computational Biology, Public Library of Science (PLoS), Vol. 18, No. 2 ( 2022-2-18), p. e1009871-
Abstract:
Spider venom GDPD-like phospholipases D ( SicTox ) have been identified to be one of the major toxins in recluse spider venom. They are divided into two major clades: the α clade and the β clade. Most α clade toxins present high activity against lipids with choline head groups such as sphingomyelin, while activities in β clade toxins vary and include preference for substrates containing ethanolamine headgroups ( Sicarius terrosus , St_βIB1). A structural comparison of available structures of phospholipases D (PLDs) reveals a conserved aromatic cage in the α clade. To test the potential influence of the aromatic cage on membrane-lipid specificity we performed molecular dynamics (MD) simulations of the binding of several PLDs onto lipid bilayers containing choline headgroups; two SicTox from the α clade, Loxosceles intermedia αIA1 (Li_αIA) and Loxosceles laeta αIII1 (Ll_αIII1), and one from the β clade, St_βIB1. The simulation results reveal that the aromatic cage captures a choline-headgroup and suggest that the cage plays a major role in lipid specificity. We also simulated an engineered St_βIB1, where we introduced the aromatic cage, and this led to binding with choline-containing lipids. Moreover, a multiple sequence alignment revealed the conservation of the aromatic cage among the α clade PLDs. Here, we confirmed that the i-face of α and β clade PLDs is involved in their binding to choline and ethanolamine-containing bilayers, respectively. Furthermore, our results suggest a major role in choline lipid recognition of the aromatic cage of the α clade PLDs. The MD simulation results are supported by in vitro liposome binding assay experiments.
Type of Medium:
Online Resource
ISSN:
1553-7358
DOI:
10.1371/journal.pcbi.1009871
DOI:
10.1371/journal.pcbi.1009871.g001
DOI:
10.1371/journal.pcbi.1009871.g002
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10.1371/journal.pcbi.1009871.g003
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10.1371/journal.pcbi.1009871.g004
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10.1371/journal.pcbi.1009871.g005
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10.1371/journal.pcbi.1009871.g006
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10.1371/journal.pcbi.1009871.g007
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10.1371/journal.pcbi.1009871.g008
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10.1371/journal.pcbi.1009871.g009
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10.1371/journal.pcbi.1009871.g010
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10.1371/journal.pcbi.1009871.t001
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10.1371/journal.pcbi.1009871.t002
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10.1371/journal.pcbi.1009871.t003
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10.1371/journal.pcbi.1009871.t004
DOI:
10.1371/journal.pcbi.1009871.t005
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10.1371/journal.pcbi.1009871.s001
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10.1371/journal.pcbi.1009871.s002
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10.1371/journal.pcbi.1009871.s003
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10.1371/journal.pcbi.1009871.s004
DOI:
10.1371/journal.pcbi.1009871.s005
DOI:
10.1371/journal.pcbi.1009871.s006
DOI:
10.1371/journal.pcbi.1009871.s007
DOI:
10.1371/journal.pcbi.1009871.s008
DOI:
10.1371/journal.pcbi.1009871.s009
DOI:
10.1371/journal.pcbi.1009871.s010
DOI:
10.1371/journal.pcbi.1009871.s011
DOI:
10.1371/journal.pcbi.1009871.s012
DOI:
10.1371/journal.pcbi.1009871.s013
DOI:
10.1371/journal.pcbi.1009871.r001
DOI:
10.1371/journal.pcbi.1009871.r002
DOI:
10.1371/journal.pcbi.1009871.r003
DOI:
10.1371/journal.pcbi.1009871.r004
DOI:
10.1371/journal.pcbi.1009871.r005
DOI:
10.1371/journal.pcbi.1009871.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2193340-6
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