Characterization of TRIM5α trimerization and its contribution to human immunodeficiency virus capsid binding

The coiled-coil domain of the tripartite motif (TRIM) family protein TRIM5 alpha is required for trimerization and function as an antiretroviral restriction factor. Unlike the coiled-coil regions of other related TRIM proteins, the coiled coil of TRIM5 alpha is not sufficient for multimerization. The linker region between the coiled-coil and B30.2 domains is necessary for efficient TRIM5 alpha trimerization. Most of the hydrophilic residues predicted to be located on the surface-exposed face of the coiled coil can be altered without compromising TRIM5 alpha antiviral activity against human immunodeficiency virus (HIV-1). However, changes that disrupt TRIM5 alpha trimerization proportionately affect the ability of TRIM5 alpha to bind HIV-1 capsid complexes. Therefore, TRIM5 alpha trimerization makes a major contribution to its avidity for the retroviral capsid, and to the ability to restrict virus infection. (c) 2006 Elsevier Inc. All rights reserved.