Cryoelectron tomography of HIV-1 envelope spikes: further evidence for tripod-like legs.

A detailed understanding of the morphology of the HIV-1 envelope (Env) spike is key to understanding viral pathogenesis and for informed vaccine design. We have previously presented a cryoelectron microscopic tomogram (cryoET) of the Env spikes on SIV virions. Several structural features were noted...

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Autores principales:	Ping Zhu, Hanspeter Winkler, Elena Chertova, Kenneth A Taylor, Kenneth H Roux
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/1dd0047919a04478aa017cc38150eaf3
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spelling	oai:doaj.org-article:1dd0047919a04478aa017cc38150eaf32021-11-25T05:47:27ZCryoelectron tomography of HIV-1 envelope spikes: further evidence for tripod-like legs.1553-73661553-737410.1371/journal.ppat.1000203https://doaj.org/article/1dd0047919a04478aa017cc38150eaf32008-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19008954/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374A detailed understanding of the morphology of the HIV-1 envelope (Env) spike is key to understanding viral pathogenesis and for informed vaccine design. We have previously presented a cryoelectron microscopic tomogram (cryoET) of the Env spikes on SIV virions. Several structural features were noted in the gp120 head and gp41 stalk regions. Perhaps most notable was the presence of three splayed legs projecting obliquely from the base of the spike head toward the viral membrane. Subsequently, a second 3D image of SIV spikes, also obtained by cryoET, was published by another group which featured a compact vertical stalk. We now report the cryoET analysis of HIV-1 virion-associated Env spikes using enhanced analytical cryoET procedures. More than 2,000 Env spike volumes were initially selected, aligned, and sorted into structural classes using algorithms that compensate for the "missing wedge" and do not impose any symmetry. The results show varying morphologies between structural classes: some classes showed trimers in the head domains; nearly all showed two or three legs, though unambiguous three-fold symmetry was not observed either in the heads or the legs. Subsequently, clearer evidence of trimeric head domains and three splayed legs emerged when head and leg volumes were independently aligned and classified. These data show that HIV-1, like SIV, also displays the tripod-like leg configuration, and, unexpectedly, shows considerable gp41 leg flexibility/heteromorphology. The tripod-like model for gp41 is consistent with, and helps explain, many of the unique biophysical and immunological features of this region.Ping ZhuHanspeter WinklerElena ChertovaKenneth A TaylorKenneth H RouxPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 4, Iss 11, p e1000203 (2008)
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 Ping Zhu Hanspeter Winkler Elena Chertova Kenneth A Taylor Kenneth H Roux Cryoelectron tomography of HIV-1 envelope spikes: further evidence for tripod-like legs.
description	A detailed understanding of the morphology of the HIV-1 envelope (Env) spike is key to understanding viral pathogenesis and for informed vaccine design. We have previously presented a cryoelectron microscopic tomogram (cryoET) of the Env spikes on SIV virions. Several structural features were noted in the gp120 head and gp41 stalk regions. Perhaps most notable was the presence of three splayed legs projecting obliquely from the base of the spike head toward the viral membrane. Subsequently, a second 3D image of SIV spikes, also obtained by cryoET, was published by another group which featured a compact vertical stalk. We now report the cryoET analysis of HIV-1 virion-associated Env spikes using enhanced analytical cryoET procedures. More than 2,000 Env spike volumes were initially selected, aligned, and sorted into structural classes using algorithms that compensate for the "missing wedge" and do not impose any symmetry. The results show varying morphologies between structural classes: some classes showed trimers in the head domains; nearly all showed two or three legs, though unambiguous three-fold symmetry was not observed either in the heads or the legs. Subsequently, clearer evidence of trimeric head domains and three splayed legs emerged when head and leg volumes were independently aligned and classified. These data show that HIV-1, like SIV, also displays the tripod-like leg configuration, and, unexpectedly, shows considerable gp41 leg flexibility/heteromorphology. The tripod-like model for gp41 is consistent with, and helps explain, many of the unique biophysical and immunological features of this region.
format	article
author	Ping Zhu Hanspeter Winkler Elena Chertova Kenneth A Taylor Kenneth H Roux
author_facet	Ping Zhu Hanspeter Winkler Elena Chertova Kenneth A Taylor Kenneth H Roux
author_sort	Ping Zhu
title	Cryoelectron tomography of HIV-1 envelope spikes: further evidence for tripod-like legs.
title_short	Cryoelectron tomography of HIV-1 envelope spikes: further evidence for tripod-like legs.
title_full	Cryoelectron tomography of HIV-1 envelope spikes: further evidence for tripod-like legs.
title_fullStr	Cryoelectron tomography of HIV-1 envelope spikes: further evidence for tripod-like legs.
title_full_unstemmed	Cryoelectron tomography of HIV-1 envelope spikes: further evidence for tripod-like legs.
title_sort	cryoelectron tomography of hiv-1 envelope spikes: further evidence for tripod-like legs.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/1dd0047919a04478aa017cc38150eaf3
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Cryoelectron tomography of HIV-1 envelope spikes: further evidence for tripod-like legs.

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