A trimer of dimers is the basic building block for human immunodeficiency virus-1 capsid assembly

Biochemistry
Manuel TsiangRoman Sakowicz

Abstract

Human immunodeficiency virus-1 (HIV-1) capsid protein (CA) has become a target of antiviral drug design in recent years. The recognition that binding of small molecules to the CA protein can result in the perturbation of capsid assembly or disassembly has led to mathematical modeling of the process. Although a number of capsid assembly models have been developed using biophysical parameters of the CA protein obtained experimentally, there is currently no model of CA polymerization that can be practically used to analyze in vitro CA polymerization data to facilitate drug discovery. Herein, we describe an equilibrium model of CA polymerization for the kinetic analysis of in vitro assembly of CA into polymer tubes. This new mathematical model has been used to assess whether a triangular trimer of dimers rather than a hexagonal hexamer can be the basic capsomere building block of CA polymer. The model allowed us to quantify for the first time the affinity for each of the four crucial interfaces involved in the polymerization process and indicated that the trimerization of CA dimers is a relatively slow step in CA polymerization in vitro. For wild-type CA, these four interfaces include the interface between two monomers of a CA dime...Continue Reading

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Citations

Mar 9, 2013·PloS One·Magdeleine HungRoman Sakowicz
Jun 9, 2014·The Journal of Chemical Physics·Matthew R Perkett, Michael F Hagan
Dec 23, 2015·Biochemistry·Daisuke SatoMasamichi Ikeguchi
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Jun 25, 2015·Journal of Chemical Information and Modeling·Fangqiang Zhu, Bo Chen
Jun 28, 2019·Journal of the American Chemical Society·Alexander J PakGregory A Voth

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