| dc.creator |
Suárez, Tatiana |
|
| dc.creator |
Gallaher, William R. |
|
| dc.creator |
Agirre, Aitziber |
|
| dc.creator |
Goñi, Félix M. |
|
| dc.creator |
Nieva, José L. |
|
| dc.date |
2008-04-14T10:22:49Z |
|
| dc.date |
2008-04-14T10:22:49Z |
|
| dc.date |
2000-09 |
|
| dc.date.accessioned |
2017-01-31T01:02:14Z |
|
| dc.date.available |
2017-01-31T01:02:14Z |
|
| dc.identifier |
Journal of Virology 74(17): 8038–8047 (2000) |
|
| dc.identifier |
1098-5514 |
|
| dc.identifier |
http://hdl.handle.net/10261/3562 |
|
| dc.identifier.uri |
http://dspace.mediu.edu.my:8181/xmlui/handle/10261/3562 |
|
| dc.description |
10 páginas, 8 figuras, 3 tablas. |
|
| dc.description |
We have identified a region within the ectodomain of the fusogenic human immunodeficiency virus type 1
(HIV-1) gp41, different from the fusion peptide, that interacts strongly with membranes. This conserved
sequence, which immediately precedes the transmembrane anchor, is not highly hydrophobic according to the
Kyte-Doolittle hydropathy prediction algorithm, yet it shows a high tendency to partition into the membrane
interface, as revealed by the Wimley-White interfacial hydrophobicity scale. We have investigated here the
membrane effects induced by NH2-DKWASLWNWFNITNWLWYIK-CONH2 (HIVc), the membrane interfacepartitioning
region at the C terminus of the gp41 ectodomain, in comparison to those caused by NH2-
AVGIGALFLGFLGAAGSTMGARS-CONH2 (HIVn), the fusion peptide at the N terminus of the subunit. Both
HIVc and HIVn were seen to induce membrane fusion and permeabilization, although lower doses of HIVc were
required for comparable effects to be detected. Experiments in which equimolar mixtures of HIVc and HIVn
were used indicated that both peptides may act in a cooperative way. Peptide-membrane and peptide-peptide
interactions underlying those effects were further confirmed by analyzing the changes in fluorescence of peptide
Trp residues. Replacement of the first three Trp residues by Ala, known to render a defective gp41 phenotype
unable to mediate both cell-cell fusion and virus entry, also abrogated the HIVc ability to induce membrane
fusion or form complexes with HIVn but not its ability to associate with vesicles. Hydropathy analysis indicated
that the presence of two membrane-partitioning stretches separated by a collapsible intervening sequence is a
common structural motif among other viral envelope proteins. Moreover, sequences with membrane surfaceresiding
residues preceding the transmembrane anchor appeared to be a common feature in viral fusion
proteins of several virus families. According to our experimental results, such a feature might be related to
their fusogenic function. |
|
| dc.description |
T.S. and A.A. are recipients of predoctoral fellowships from the
Basque Government. This work was supported by DGCYT (grant
PB96-0171), the Basque Government (PI 96-46; EX-1998-28; PI-1998-
32), and the University of the Basque Country (UPV 042.310-EA085/
97; UPV 042.310-G03/98). Support to W.R.G. includes senior fellowship
1F32AI08549 and grant 1R01DE10862 from the National
Institutes of Health of the United States. |
|
| dc.description |
Peer reviewed |
|
| dc.format |
160242 bytes |
|
| dc.format |
application/pdf |
|
| dc.language |
eng |
|
| dc.publisher |
American Society for Microbiology |
|
| dc.relation |
http://jvi.asm.org/cgi/content/short/74/17/8038 |
|
| dc.rights |
closedAccess |
|
| dc.title |
Membrane Interface-Interacting Sequences within the Ectodomain of the Human Immunodeficiency Virus Type 1 Envelope Glycoprotein: Putative Role during Viral Fusion |
|
| dc.type |
Artículo |
|