A Tyrosine-Sulfated CCR5-Mimetic Peptide Promotes Conformational Transitions in the HIV-1 Envelope Glycoprotein

• DOI: 10.1128/jvi.00630-11
• Publication Date: 2011-05-26T02:51:49Z
• Authors: Jo Ann Kwong; Tatyana Dorfman; Brian D. Quinlan; Jessica J. Chiang; Asim A. Ahmed; Hyeryun Choe; Michael Farzan
• Keywords: Trimer; Avidity; V3 loop

ABSTRACT The HIV-1 envelope glycoprotein is a trimeric complex of heterodimers composed surface glycoprotein, gp120, and transmembrane component, gp41. association this with CD4 stabilizes the coreceptor-binding site gp120 promotes exposure gp41 helical region 1 (HR1). Here, we show that 15-amino-acid peptide mimetic coreceptor CCR5 fused to dimeric antibody Fc domain (CCR5mim-Ig) bound two molecules per by itself promoted HR1 exposure. CCR5mim-Ig also stabilized CD4-mimetic glycoprotein. A fusion CD4- CCR5-mimetic peptides, DM1, neutralized R5, R5X4, X4 isolates comparably CD4, they did so markedly more efficiently than either alone. Our data indicate potency DM1-Ig derives from its avidity for trimer bidirectional induction receptor-mimetic components. DM1 has significant advantages over other inhibitors target both CD4-binding sites, it may serve as lead new class inhibitor peptides.