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Journal of Virology, July 2001, p. 6682-6686, Vol. 75, No. 14
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.14.6682-6686.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Structural Flexibility and Functional Valence of CD4-IgG2 (PRO 542): Potential for Cross-Linking Human Immunodeficiency Virus Type 1 Envelope Spikes

Ping Zhu,1 William C. Olson,2 and Kenneth H. Roux1,*

Department of Biological Science and Structural Biology Program, Florida State University, Tallahassee, Florida 32306,1 and Progenics Pharmaceuticals, Inc., Tarrytown, New York 105912

Received 16 February 2001/Accepted 18 April 2001

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-gamma 2, a divalent CD4-immunoglobulin fusion protein, was evaluated in parallel. Whereas CD4-gamma 2-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-gamma 2 has significant potential to cross-link gp120-gp41 trimers on the virion surface, suggesting a mechanism for the heightened antiviral activity of CD4-IgG2.

* Corresponding author. Mailing address: Department of Biological Science, Biology Unit I, Florida State University, Tallahassee, FL 32306-4370. Phone: (850) 644-5037. Fax: (850) 644-0481. E-mail: roux{at}bio.fsu.edu.

Journal of Virology, July 2001, p. 6682-6686, Vol. 75, No. 14
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.14.6682-6686.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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