Reconsidering the Model of Trim5α Assembly: The Role of the Linker2 (l2) Region in Trim5α Assembly

摘要: 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 hexameric assembly can superimpose on the lattice HIV-1 capsid. mechanism underlying the self-association and molecular determinants remain to be completely understood. In this study, we show Linker 2 (L2) region of TRIM5rh is important for dimerization higher order self-association, both which are independent processes. Additionally, fluorescence resonance energy transfer (FRET) analysis suggests an antiparallel dimer configuration the basic unit TRIM5α, consistent with recently published crystal structure CCL2 TRIM25 Sanchez et al. We propose homology model fragment of TRIM5α based on region. In Helix 3 L2 folds back onto 1 (CC domain), possibly ensuring correct binding SPRY domain to core. These reveal previously unknown determinants in govern of TRIM5α.