Charge-surrounded pockets and electrostatic interactions with small ions modulate the activity of retroviral fusion proteins.

Refolding of viral class-1 membrane fusion proteins from a native state to a trimer-of-hairpins structure promotes entry of viruses into cells. Here we present the structure of the bovine leukaemia virus transmembrane glycoprotein (TM) and identify a group of asparagine residues at the membrane-dist...

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Autores principales:	Daniel Lamb, Alexander W Schüttelkopf, Daan M F van Aalten, David W Brighty
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/899a707dd69c4f9fa149105ecc6cce1e
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spelling	oai:doaj.org-article:899a707dd69c4f9fa149105ecc6cce1e2021-11-18T06:03:38ZCharge-surrounded pockets and electrostatic interactions with small ions modulate the activity of retroviral fusion proteins.1553-73661553-737410.1371/journal.ppat.1001268https://doaj.org/article/899a707dd69c4f9fa149105ecc6cce1e2011-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21304939/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Refolding of viral class-1 membrane fusion proteins from a native state to a trimer-of-hairpins structure promotes entry of viruses into cells. Here we present the structure of the bovine leukaemia virus transmembrane glycoprotein (TM) and identify a group of asparagine residues at the membrane-distal end of the trimer-of-hairpins that is strikingly conserved among divergent viruses. These asparagines are not essential for surface display of pre-fusogenic envelope. Instead, substitution of these residues dramatically disrupts membrane fusion. Our data indicate that, through electrostatic interactions with a chloride ion, the asparagine residues promote assembly and profoundly stabilize the fusion-active structures that are required for viral envelope-mediated membrane fusion. Moreover, the BLV TM structure also reveals a charge-surrounded hydrophobic pocket on the central coiled coil and interactions with basic residues that cluster around this pocket are critical to membrane fusion and form a target for peptide inhibitors of envelope function. Charge-surrounded pockets and electrostatic interactions with small ions are common among class-1 fusion proteins, suggesting that small molecules that specifically target such motifs should prevent assembly of the trimer-of-hairpins and be of value as therapeutic inhibitors of viral entry.Daniel LambAlexander W SchüttelkopfDaan M F van AaltenDavid W BrightyPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 7, Iss 2, p e1001268 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Daniel Lamb Alexander W Schüttelkopf Daan M F van Aalten David W Brighty Charge-surrounded pockets and electrostatic interactions with small ions modulate the activity of retroviral fusion proteins.
description	Refolding of viral class-1 membrane fusion proteins from a native state to a trimer-of-hairpins structure promotes entry of viruses into cells. Here we present the structure of the bovine leukaemia virus transmembrane glycoprotein (TM) and identify a group of asparagine residues at the membrane-distal end of the trimer-of-hairpins that is strikingly conserved among divergent viruses. These asparagines are not essential for surface display of pre-fusogenic envelope. Instead, substitution of these residues dramatically disrupts membrane fusion. Our data indicate that, through electrostatic interactions with a chloride ion, the asparagine residues promote assembly and profoundly stabilize the fusion-active structures that are required for viral envelope-mediated membrane fusion. Moreover, the BLV TM structure also reveals a charge-surrounded hydrophobic pocket on the central coiled coil and interactions with basic residues that cluster around this pocket are critical to membrane fusion and form a target for peptide inhibitors of envelope function. Charge-surrounded pockets and electrostatic interactions with small ions are common among class-1 fusion proteins, suggesting that small molecules that specifically target such motifs should prevent assembly of the trimer-of-hairpins and be of value as therapeutic inhibitors of viral entry.
format	article
author	Daniel Lamb Alexander W Schüttelkopf Daan M F van Aalten David W Brighty
author_facet	Daniel Lamb Alexander W Schüttelkopf Daan M F van Aalten David W Brighty
author_sort	Daniel Lamb
title	Charge-surrounded pockets and electrostatic interactions with small ions modulate the activity of retroviral fusion proteins.
title_short	Charge-surrounded pockets and electrostatic interactions with small ions modulate the activity of retroviral fusion proteins.
title_full	Charge-surrounded pockets and electrostatic interactions with small ions modulate the activity of retroviral fusion proteins.
title_fullStr	Charge-surrounded pockets and electrostatic interactions with small ions modulate the activity of retroviral fusion proteins.
title_full_unstemmed	Charge-surrounded pockets and electrostatic interactions with small ions modulate the activity of retroviral fusion proteins.
title_sort	charge-surrounded pockets and electrostatic interactions with small ions modulate the activity of retroviral fusion proteins.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/899a707dd69c4f9fa149105ecc6cce1e
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Charge-surrounded pockets and electrostatic interactions with small ions modulate the activity of retroviral fusion proteins.

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