The tegumental allergen-like proteins of Schistosoma mansoni: a biochemical study of SmTAL4-TAL13

Jack Carson, Charlotte M. Thomas, Aaron McGinty, Gustavo Takata, David Timson

Research output: Contribution to journalArticle

Abstract

Schistosoma mansoni, like other trematodes, expresses a number of unusual calcium binding proteins which consist of an EF-hand domain joined to a dynein light chain-like (DLC-like) domain by a flexible linker. These proteins have been implicated in host immune responses and drug binding. Three members of this protein family from S. mansoni (SmTAL1, SmTAL2 and SmTAL3) have been well characterised biochemically. Here we characterise the remaining family members from this species (SmTAL4-13). All of these proteins form homodimers and all except SmTAL5 bind to calcium and manganese ions. SmTAL9, 10 and 11 also bind to magnesium ions. The antischistosomal drug, praziquantel interacts with SmTAL4, 5 and 8. Some family members also bind to calmodulin antagonists such as chlorpromazine and trifluoperazine. Molecular modelling suggests that all ten proteins adopt similar overall folds with the EF-hand and DLC-like domains folding discretely. Bioinformatics analyses suggest that the proteins may fall into two main categories: (i) those which bind calcium ions reversibly at the second EF-hand and may play a role in signalling (SmTAL1, 2, 8 31 and 12) and (ii) those which bind calcium ions at the first EF-hand and may play either signalling or structural roles (SmTAL7, 9, 10 and 13). The remaining proteins include those which do not bind calcium ions (SmTAL3 and 5) and three other proteins (SmTAL4, 6 and 11). The roles of these proteins are less clear, but they may also have structural roles.
Original languageEnglish
Pages (from-to)14-22
Number of pages9
JournalMolecular and Biochemical Parasitology
Volume221
DOIs
Publication statusPublished - 14 Feb 2018

Fingerprint

Schistosoma mansoni
allergens
ions
hands
proteins
calcium
trifluoperazine
chlorpromazine
praziquantel
drugs
calcium-binding proteins
calmodulin
Trematoda
bioinformatics
manganese
antagonists
magnesium
immune response

Bibliographical note

© 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/

Keywords

  • schistosomiasis
  • EF-hand
  • dynein light chain
  • calcium binding protein
  • praziquantel
  • 37 tegumental allergen protein

Cite this

Carson, Jack ; Thomas, Charlotte M. ; McGinty, Aaron ; Takata, Gustavo ; Timson, David. / The tegumental allergen-like proteins of Schistosoma mansoni: a biochemical study of SmTAL4-TAL13. In: Molecular and Biochemical Parasitology. 2018 ; Vol. 221. pp. 14-22.
@article{74e76a5a13db4f7b9de2fe2050adc9a6,
title = "The tegumental allergen-like proteins of Schistosoma mansoni: a biochemical study of SmTAL4-TAL13",
abstract = "Schistosoma mansoni, like other trematodes, expresses a number of unusual calcium binding proteins which consist of an EF-hand domain joined to a dynein light chain-like (DLC-like) domain by a flexible linker. These proteins have been implicated in host immune responses and drug binding. Three members of this protein family from S. mansoni (SmTAL1, SmTAL2 and SmTAL3) have been well characterised biochemically. Here we characterise the remaining family members from this species (SmTAL4-13). All of these proteins form homodimers and all except SmTAL5 bind to calcium and manganese ions. SmTAL9, 10 and 11 also bind to magnesium ions. The antischistosomal drug, praziquantel interacts with SmTAL4, 5 and 8. Some family members also bind to calmodulin antagonists such as chlorpromazine and trifluoperazine. Molecular modelling suggests that all ten proteins adopt similar overall folds with the EF-hand and DLC-like domains folding discretely. Bioinformatics analyses suggest that the proteins may fall into two main categories: (i) those which bind calcium ions reversibly at the second EF-hand and may play a role in signalling (SmTAL1, 2, 8 31 and 12) and (ii) those which bind calcium ions at the first EF-hand and may play either signalling or structural roles (SmTAL7, 9, 10 and 13). The remaining proteins include those which do not bind calcium ions (SmTAL3 and 5) and three other proteins (SmTAL4, 6 and 11). The roles of these proteins are less clear, but they may also have structural roles.",
keywords = "schistosomiasis, EF-hand, dynein light chain, calcium binding protein, praziquantel, 37 tegumental allergen protein",
author = "Jack Carson and Thomas, {Charlotte M.} and Aaron McGinty and Gustavo Takata and David Timson",
note = "{\circledC} 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/",
year = "2018",
month = "2",
day = "14",
doi = "10.1016/j.molbiopara.2018.02.002",
language = "English",
volume = "221",
pages = "14--22",
journal = "Molecular and Biochemical Parasitology",
issn = "0166-6851",

}

The tegumental allergen-like proteins of Schistosoma mansoni: a biochemical study of SmTAL4-TAL13. / Carson, Jack; Thomas, Charlotte M.; McGinty, Aaron; Takata, Gustavo; Timson, David.

In: Molecular and Biochemical Parasitology, Vol. 221, 14.02.2018, p. 14-22.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The tegumental allergen-like proteins of Schistosoma mansoni: a biochemical study of SmTAL4-TAL13

AU - Carson, Jack

AU - Thomas, Charlotte M.

AU - McGinty, Aaron

AU - Takata, Gustavo

AU - Timson, David

N1 - © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/

PY - 2018/2/14

Y1 - 2018/2/14

N2 - Schistosoma mansoni, like other trematodes, expresses a number of unusual calcium binding proteins which consist of an EF-hand domain joined to a dynein light chain-like (DLC-like) domain by a flexible linker. These proteins have been implicated in host immune responses and drug binding. Three members of this protein family from S. mansoni (SmTAL1, SmTAL2 and SmTAL3) have been well characterised biochemically. Here we characterise the remaining family members from this species (SmTAL4-13). All of these proteins form homodimers and all except SmTAL5 bind to calcium and manganese ions. SmTAL9, 10 and 11 also bind to magnesium ions. The antischistosomal drug, praziquantel interacts with SmTAL4, 5 and 8. Some family members also bind to calmodulin antagonists such as chlorpromazine and trifluoperazine. Molecular modelling suggests that all ten proteins adopt similar overall folds with the EF-hand and DLC-like domains folding discretely. Bioinformatics analyses suggest that the proteins may fall into two main categories: (i) those which bind calcium ions reversibly at the second EF-hand and may play a role in signalling (SmTAL1, 2, 8 31 and 12) and (ii) those which bind calcium ions at the first EF-hand and may play either signalling or structural roles (SmTAL7, 9, 10 and 13). The remaining proteins include those which do not bind calcium ions (SmTAL3 and 5) and three other proteins (SmTAL4, 6 and 11). The roles of these proteins are less clear, but they may also have structural roles.

AB - Schistosoma mansoni, like other trematodes, expresses a number of unusual calcium binding proteins which consist of an EF-hand domain joined to a dynein light chain-like (DLC-like) domain by a flexible linker. These proteins have been implicated in host immune responses and drug binding. Three members of this protein family from S. mansoni (SmTAL1, SmTAL2 and SmTAL3) have been well characterised biochemically. Here we characterise the remaining family members from this species (SmTAL4-13). All of these proteins form homodimers and all except SmTAL5 bind to calcium and manganese ions. SmTAL9, 10 and 11 also bind to magnesium ions. The antischistosomal drug, praziquantel interacts with SmTAL4, 5 and 8. Some family members also bind to calmodulin antagonists such as chlorpromazine and trifluoperazine. Molecular modelling suggests that all ten proteins adopt similar overall folds with the EF-hand and DLC-like domains folding discretely. Bioinformatics analyses suggest that the proteins may fall into two main categories: (i) those which bind calcium ions reversibly at the second EF-hand and may play a role in signalling (SmTAL1, 2, 8 31 and 12) and (ii) those which bind calcium ions at the first EF-hand and may play either signalling or structural roles (SmTAL7, 9, 10 and 13). The remaining proteins include those which do not bind calcium ions (SmTAL3 and 5) and three other proteins (SmTAL4, 6 and 11). The roles of these proteins are less clear, but they may also have structural roles.

KW - schistosomiasis

KW - EF-hand

KW - dynein light chain

KW - calcium binding protein

KW - praziquantel

KW - 37 tegumental allergen protein

U2 - 10.1016/j.molbiopara.2018.02.002

DO - 10.1016/j.molbiopara.2018.02.002

M3 - Article

VL - 221

SP - 14

EP - 22

JO - Molecular and Biochemical Parasitology

JF - Molecular and Biochemical Parasitology

SN - 0166-6851

ER -