Hydrophobic Substitutions in the First Residue of the CRAC Segment of the gp41 Protein of HIV

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• 作者：Sundaram A. Vishwanathan ; Annick Thomas ; Robert Brasseur ; Raquel F. Epand ; Eric Hunter ; Richard M. Epand
• 刊名：Biochemistry
• 出版年：2008
• 出版时间：January 8, 2008
• 年：2008
• 卷：47
• 期：1
• 页码：124 - 130
• 全文大小：281K
• 年卷期：v.47,no.1(January 8, 2008)
• ISSN：1520-4995

文摘

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 andbelieved to play a role in sequestering this protein to a cholesterol-rich domain in the membrane. Theeffects 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-typesequence (LWYIK) and another (IWYIK), the least active peptide previously studied. This correlatedwith results from studies of single mutations in the gp41 protein of HIV-1, in which L⁶⁷⁹ of the LWYIKsegment is replaced with either A or V, measuring the capability of TZM-BL HeLa-based HIV-1 indicatorcells to form syncytia. The peptides were also comparatively analyzed in silico. All together, the resultssuggest that the mode of interaction of this region of gp41 with the polar heads of membrane lipidscontributes to its cholesterol selectivity and that this is somehow related to the biological activity of theviral glycoprotein.