Structural flexibility and functional valence of CD4-IgG2 (PRO 542): potential for cross-linking human immunodeficiency virus type 1 envelope spikes.
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.
Zhu
P
P
Department of Biological Science and Structural Biology Program, Florida State University, Tallahassee, Florida 32306, USA.
Olson
W C
WC
Roux
K H
KH
D016860:CD4 Immunoadhesins / Q000378:metabolism* / Q000648:ultrastructure; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism* / Q000648:ultrastructure; D016253:Microscopy, Immunoelectron; D008958:Models, Molecular; D013329:Structure-Activity Relationship
D016860:CD4 Immunoadhesins; C096753:CD4-IgG(2); D015699:HIV Envelope Protein gp120