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Elucidation of the Rotavirus NSP4-Caveolin-1 and -Cholesterol Interactions Using Synthetic Peptides

Rotavirus (RV) NSP4, the first described viral enterotoxin, is a multifunctional glycoprotein that contributes to viral pathogenesis, morphogenesis, and replication. NSP4 binds both termini of caveolin-1 and is isolated from caveolae fractions that are rich in anionic phospholipids and cholesterol....

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Autores principales: Schroeder, Megan E., Hostetler, Heather A., Schroeder, Friedhelm, Ball, Judith M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3303745/
https://www.ncbi.nlm.nih.gov/pubmed/22500212
http://dx.doi.org/10.1155/2012/575180
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author Schroeder, Megan E.
Hostetler, Heather A.
Schroeder, Friedhelm
Ball, Judith M.
author_facet Schroeder, Megan E.
Hostetler, Heather A.
Schroeder, Friedhelm
Ball, Judith M.
author_sort Schroeder, Megan E.
collection PubMed
description Rotavirus (RV) NSP4, the first described viral enterotoxin, is a multifunctional glycoprotein that contributes to viral pathogenesis, morphogenesis, and replication. NSP4 binds both termini of caveolin-1 and is isolated from caveolae fractions that are rich in anionic phospholipids and cholesterol. These interactions indicate that cholesterol/caveolin-1 plays a role in NSP4 transport to the cell surface, which is essential to its enterotoxic activity. Synthetic peptides were utilized to identify target(s) of intervention by exploring the NSP4-caveolin-1 and -cholesterol interactions. NSP4(112–140) that overlaps the caveolin-1 binding domain and a cholesterol recognition amino acid consensus (CRAC) motif and both termini of caveolin-1 (N-caveolin-1(2–20),  (19–40) and C-caveolin-1(161–180)) were synthesized. Direct fluorescence-binding assays were employed to determine binding affinities of the NSP4-caveolin-1 peptides and cholesterol. Intracellular cholesterol alteration revealed a redistribution of NSP4 and disintegration of viroplasms. These data further imply interruption of NSP4(112–140)-N-caveolin-1(19–40) and cholesterol interactions may block NSP4 intracellular transport, hence enterotoxicity.
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spelling pubmed-33037452012-04-12 Elucidation of the Rotavirus NSP4-Caveolin-1 and -Cholesterol Interactions Using Synthetic Peptides Schroeder, Megan E. Hostetler, Heather A. Schroeder, Friedhelm Ball, Judith M. J Amino Acids Research Article Rotavirus (RV) NSP4, the first described viral enterotoxin, is a multifunctional glycoprotein that contributes to viral pathogenesis, morphogenesis, and replication. NSP4 binds both termini of caveolin-1 and is isolated from caveolae fractions that are rich in anionic phospholipids and cholesterol. These interactions indicate that cholesterol/caveolin-1 plays a role in NSP4 transport to the cell surface, which is essential to its enterotoxic activity. Synthetic peptides were utilized to identify target(s) of intervention by exploring the NSP4-caveolin-1 and -cholesterol interactions. NSP4(112–140) that overlaps the caveolin-1 binding domain and a cholesterol recognition amino acid consensus (CRAC) motif and both termini of caveolin-1 (N-caveolin-1(2–20),  (19–40) and C-caveolin-1(161–180)) were synthesized. Direct fluorescence-binding assays were employed to determine binding affinities of the NSP4-caveolin-1 peptides and cholesterol. Intracellular cholesterol alteration revealed a redistribution of NSP4 and disintegration of viroplasms. These data further imply interruption of NSP4(112–140)-N-caveolin-1(19–40) and cholesterol interactions may block NSP4 intracellular transport, hence enterotoxicity. Hindawi Publishing Corporation 2012 2012-03-01 /pmc/articles/PMC3303745/ /pubmed/22500212 http://dx.doi.org/10.1155/2012/575180 Text en Copyright © 2012 Megan E. Schroeder et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Schroeder, Megan E.
Hostetler, Heather A.
Schroeder, Friedhelm
Ball, Judith M.
Elucidation of the Rotavirus NSP4-Caveolin-1 and -Cholesterol Interactions Using Synthetic Peptides
title Elucidation of the Rotavirus NSP4-Caveolin-1 and -Cholesterol Interactions Using Synthetic Peptides
title_full Elucidation of the Rotavirus NSP4-Caveolin-1 and -Cholesterol Interactions Using Synthetic Peptides
title_fullStr Elucidation of the Rotavirus NSP4-Caveolin-1 and -Cholesterol Interactions Using Synthetic Peptides
title_full_unstemmed Elucidation of the Rotavirus NSP4-Caveolin-1 and -Cholesterol Interactions Using Synthetic Peptides
title_short Elucidation of the Rotavirus NSP4-Caveolin-1 and -Cholesterol Interactions Using Synthetic Peptides
title_sort elucidation of the rotavirus nsp4-caveolin-1 and -cholesterol interactions using synthetic peptides
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3303745/
https://www.ncbi.nlm.nih.gov/pubmed/22500212
http://dx.doi.org/10.1155/2012/575180
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