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Journal of Virology, September 2000, p. 8038-8047, Vol. 74, No. 17
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Membrane Interface-Interacting Sequences within the Ectodomain of
the Human Immunodeficiency Virus Type 1 Envelope Glycoprotein: Putative
Role during Viral Fusion
Tatiana
Suárez,1
William R.
Gallaher,2
Aitziber
Agirre,1
Félix M.
Goñi,1 and
José L.
Nieva1,*
Unidad de Biofísica (CSIC-UPV/EHU)
and Departamento de Bioquímica, Universidad del País
Vasco, 48080 Bilbao, Spain,1 and
Department of Microbiology, Immunology and Parasitology,
Louisiana State University Health Sciences Center, New Orleans,
Louisiana 701122
Received 27 March 2000/Accepted 30 May 2000
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 interface-partitioning 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 surface-residing 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.
*
Corresponding author. Mailing address: Unidad de
Biofísica (CSIC-UPV/EHU) y Departamento de Bioquímica,
Universidad del País Vasco, Aptdo. 644, 48080 Bilbao, Spain.
Phone: 34 94 6012615. Fax: 34 94 4648500. E-mail:
GBPNIESJ{at}lg.ehu.es.
Journal of Virology, September 2000, p. 8038-8047, Vol. 74, No. 17
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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