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Biotech / Medical : progenics -- Ignore unavailable to you. Want to Upgrade?

To: keokalani'nui who wrote (55)	7/29/2001 12:58:10 PM
From: tuck	Read Replies (1) \| Respond to of 139

Parking: >>Structural flexibility and functional valence of CD4-IgG2 (PRO 542): potential for cross-linking human immunodeficiency virus type 1 envelope spikes. J Virol 2001 Jul;75(14):6682-6 (ISSN: 0022-538X) Zhu P; Olson WC; Roux KH [Find other articles with these Authors] Department of Biological Science and Structural Biology Program, Florida State University, Tallahassee, Florida 32306, USA. CD4-immunoglobulin G2 (CD4-IgG2) incorporates four copies of the D1D2 domains of CD4 into an antibody-like molecule that potently neutralizes primary human immunodeficiency virus type 1. Here electron microscopy was used to explore the structure and functional valence of CD4-IgG2 in complex with gp120. CD4-gamma2, a divalent CD4-immunoglobulin fusion protein, was evaluated in parallel. Whereas CD4-gamma2-gp120 complexes adopted a simple Y-shaped structure, CD4-IgG2-gp120 complexes consisted of four gp120s arrayed about a central CD4-IgG2 molecule, a structure more reminiscent of complement C1q. Molecular modeling corroborated the electron microscopy data and further indicated that CD4-IgG2 but not CD4-gamma2 has significant potential to cross-link gp120-gp41 trimers on the virion surface, suggesting a mechanism for the heightened antiviral activity of CD4-IgG2.>> snip >>Mapping the determinants of the CCR5 amino-terminal sulfopeptide interaction with soluble human immunodeficiency virus type 1 gp120-CD4 complexes. J Virol 2001 Jun;75(12):5541-9 (ISSN: 0022-538X) Cormier EG; Tran DN; Yukhayeva L; Olson WC; Dragic T [Find other articles with these Authors] Microbiology and Immunology Department, Albert Einstein College of Medicine, Bronx, New York 10461, USA. CD4 and CCR5 mediate fusion and entry of R5 human immunodeficiency virus type 1 (HIV-1) strains. Sulfotyrosine and other negatively charged residues in the CCR5 amino-terminal domain (Nt) are crucial for gp120 binding and viral entry. We previously showed that a soluble gp120-CD4 complex specifically binds to a peptide corresponding to CCR5 Nt residues 2 to 18, with sulfotyrosines in positions 10 and 14. This sulfopeptide also inhibits soluble gp120-CD4 binding to cell surface CCR5 as well as infection by an R5 virus. Here we show that residues 10 to 18 constitute the minimal domain of the CCR5 Nt that is able to specifically interact with soluble gp120-CD4 complexes. In addition to sulfotyrosines in positions 10 and 14, negatively charged residues in positions 11 and 18 participate in this interaction. Furthermore, the CCR5 Nt binds to a CD4-induced surface on gp120 that is composed of conserved residues in the V3 loop stem and the C4 domain. Binding of gp120 to cell surface CCR5 is further influenced by residues in the crown of the V3 loop, C1, C2, and C3. Our data suggest that gp120 docking to CCR5 is a multistep process involving several independent regions of the envelope glycoprotein and the coreceptor.<< snip Cheers, Tuck