Date of Award


Degree Type


Degree Name

Master of Science (MS)


Microbiology and Immunology


The TRIM5α protein from rhesus macaques (TRIM5αrh) exhibits a remarkable ability to potently inhibit infection by Human Immunodeficiency Virus Type-1 (HIV-1). Extensive studies have shown that TRIM5α is capable of self-associating at many levels, eventually leading to the formation of a hexameric assembly that can superimpose on the hexameric lattice of the HIV-1 capsid. The mechanism underlying the self-association of TRIM5α and the molecular determinants of self-association remain to be completely understood. In this study, we show that the Linker 2 (L2) region of TRIM5rh is important for dimerization and higher order self-association, both of which are independent processes. Additionally, fluorescence resonance energy transfer (FRET) analysis suggests that an antiparallel dimer configuration is the basic unit of TRIM5α, consistent with the recently published crystal structure of the CCL2 region of TRIM25 by Sanchez et al. We propose a homology model of the CCL2 fragment of TRIM5α based on the structure of the TRIM25 CCL2 region. In this model the Helix 3 of the L2 region folds back onto Helix 1 (CC domain), possibly ensuring correct binding of the SPRY domain to the HIV-1 core. These studies reveal previously unknown determinants in the L2 region that govern self-association of TRIM5α.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Included in

Virology Commons