Hydrophobic Substitutions In The First Residue Of The Crac Segment Of The Gp41 Protein Of Hiv

[en] We investigated the peptides N-acetyl-AWYIK-amide and N-acetyl-VWYIK-amide corresponding to single amino acid substitutions in LWYIK, a segment found in the gp41 protein of HIV and believed to play a role in sequestering this protein to a cholesterol-rich domain in the membrane. The effects of these peptides on the thermotropic phase transitions of 1-stearoyl-2-oleoylphosphatidylcholine (SOPC) and mixtures of SOPC and cholesterol were intermediate between that having the wild-type sequence (LWYIK) and another (IWYIK), the least active peptide previously studied. This correlated with results from studies of single mutations in the gp41 protein of HIV-1, in which L679 of the LWYIK segment is replaced with either A or V, measuring the capability of TZM-BL HeLa-based HIV-1 indicator cells to form syncytia. The peptides were also comparatively analyzed in silico. All together, the results suggest that the mode of interaction of this region of gp41 with the polar heads of membrane lipids contributes to its cholesterol selectivity and that this is somehow related to the biological activity of the viral glycoprotein.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Vishwanathan, Sa.

Thomas, Annick ; Université de Liège - ULiège > Chimie et bio-industries > Centre de Bio. Fond. - Section de Biologie moléc. et numér.

Brasseur, Robert ; Université de Liège - ULiège > Gembloux Agro-Bio Tech

Epand, Rf.

Hunter, E.

Epand, Rm.

Language :

English

Title :

Hydrophobic Substitutions In The First Residue Of The Crac Segment Of The Gp41 Protein Of Hiv

Publication date :

2008

Journal title :

Biochemistry

ISSN :

0006-2960

eISSN :

1520-4995

Publisher :

American Chemical Society, Washington, United States - District of Columbia

Volume :

Issue :

Pages :

124-130
124-30

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 23 June 2010

Statistics

Number of views

44 (0 by ULiège)

Number of downloads

0 (0 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

Bibliography

Salzwedel, K., West, J. T., and Hunter, E. (1999) A conserved tryptophan-rich motif in the membrane-proximal region of the human immunodeficiency virus type 1 gp41 ectodomain is important for Env-mediated fusion and virus infectivity, J. Virol. 73, 2469-2480.
Bellamy-McIntyre, A. K., Lay, C. S., Baar, S., Maerz, A. L., Talbo, G. H., Drummer, H. E., and Poumbourios, P. (2007) Functional links between the fusion peptide-proximal polar segment and membrane-proximal region of human immunodeficiency virus gp41 in distinct phases of membrane fusion, J. Biol. Chem. 282, 23104-23116.
Vincent, N., Genin, C., and Malvoisin, E. (2002) Identification of a conserved domain of the HIV-1 transmembrane protein gp41 which interacts with cholesteryl groups, Biochim. Biophys. Acta 1567, 157-164.
Epand, R. M., Sayer, B. G., and Epand, R. F. (2003) Peptide-induced formation of cholesterol-rich domains, Biochemistry. 42, 14677-14689.
Li, H., and Papadopoulos, V. (1998) Peripheral-type benzodiazepine receptor function in cholesterol transport. Identification of a putative cholesterol recognition/interaction amino acid sequence and consensus pattern, Endocrinology 139, 4991-4997.
Palmer, M. (2004) Cholesterol and the activity of bacterial toxins, FEMS Microbiol. Lett. 238, 281-289.
Epand, R. F., Thomas, A., Brasseur, R., Vishwanathan, S. A., Hunter, E., and Epand, R. M. (2006) Juxtamembrane protein segments that contribute to recruitment of cholesterol into domains, Biochemistry 45, 6105-6114.
Privalov, G., Kavina, V., Freire, E., and Privalov, P. L. (1995) Precise scanning calorimeter for studying thermal properties of biological macromolecules in dilute solution, Anal. Biochem. 232, 79-85.
Thomas, A., Deshayes, S., Decaffmeyer, M., Van Eyck, M. H., Charloteaux, B., and Brasseur, R. (2006) Prediction of peptide structure: How far are we? Proteins 65, 889-897.
Lins, L., Brasseur, R., De Pauw, M., Van Biervliet, J. P., Ruysschaert, J. M., Rosseneu, M., and Vanloo, B. (1995) Helix-helix interactions in reconstituted high-density lipoproteins, Biochim. Biophys. Acta 1258, 10-18.
Leach, A. R. (1996) van der Waals Interactions, in Molecular Modelling: Principles and Applications (Leach, A. R., Ed.) pp 171-177, Longman Ltd., Harlow, England.
Moult, J., and James, M. N. (1986) An algorithm for determining the conformation of polypeptide segments in proteins by systematic search, Proteins 1, 146-163.
Thomas, A., Milon, A., and Brasseur, R. (2004) Partial atomic charges of amino acids in proteins, Proteins 56, 102-109.
Brasseur, R. (1995) Simulating the folding of small proteins by use of the local minimum energy and the free solvation energy yields native-like structures, J. Mol. Graphics 13, 312-322.
Lins, L., Thomas, A., and Brasseur, R. (2003) Analysis of accessible surface of residues in proteins, Protein Sci. 12, 1406-1417.
Ducarme, P., Rahman, M., and Brasseur, R. (1998) IMPALA: A simple restraint field to simulate the biological membrane in molecular structure studies, Proteins. 30, 357-371.
Wei, X., Decker, J. M., Liu, H., Zhang, Z., Arani, R. B., Kilby, J. M., Saag, M. S., Wu, X., Shaw, G. M., and Kappes, J. C. (2002) Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy, Antimicrob. Agents. Chemother. 46, 1896-1905.
Kimpton, J., and Emerman, M. (1992) Detection of replication-competent and pseudotyped human immunodeficiency virus with a sensitive cell line on the basis of activation of an integrated beta-galactosidase gene, J. Virol. 66, 2232-2239.
Epand, R. M. (2007) Detecting the presence of membrane domains using DSC, Biophys. Chem. 126, 197-200.
Epand, R. M., Bach, D., Borochov, N., and Wachtel, E. (2000) Cholesterol crystalline polymorphism and the solubility of cholesterol in phosphatidylserine, Biophys. J. 78, 866-873.
Loomis, C. R., Shipley, G. G., and Small, D. M. (1979) The phase behavior of hydrated cholesterol, J. Lipid Res. 20, 525-535.
Epand, R. M. (2004) Do proteins facilitate the formation of cholesterol-rich domains? Biochim. Biophys. Acta 1666, 227-238.
Brasseur, R. (1991) Differentiation of lipid-associating helices by use of three-dimensional molecular hydrophobicity potential calculations, J. Biol. Chem. 266, 16120-16127.
Zwick, M. B., Jensen, R., Church, S., Wang, M., Stiegler, G., Kunert, R., Katinger, H., and Burton, D. R. (2005) Anti-human immunodeficiency virus type 1 (HIV-1) antibodies 2F5 and 4E10 require surprisingly few crucial residues in the membrane-proximal external region of glycoprotein gp41 to neutralize HIV-1, J. Virol. 79, 1252-1261.
Lin, X., Derdeyn, C. A., Blumenthal, R., West, J., and Hunter, E. (2003) Progressive truncations C terminal to the membrane-spanning domain of simian immunodeficiency virus Env reduce fusogenicity and increase concentration dependence of Env for fusion, J. Virol. 77, 7067-7077.
Thomas, A., Milon, A., and Brasseur, R. (2004) Partial atomic charges of amino acids in proteins, Proteins 56, 102-109.