Characterization of TRIM5alpha trimerization and its contribution to human immunodeficiency virus capsid binding.
The coiled-coil domain of the tripartite motif (TRIM) family protein TRIM5alpha 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 TRIM5alpha is not sufficient for multimerization. The linker region between the coiled-coil and B30.2 domains is necessary for efficient TRIM5alpha trimerization. Most of the hydrophilic residues predicted to be located on the surface-exposed face of the coiled coil can be altered without compromising TRIM5alpha antiviral activity against human immunodeficiency virus (HIV-1). However, changes that disrupt TRIM5alpha trimerization proportionately affect the ability of TRIM5alpha to bind HIV-1 capsid complexes. Therefore, TRIM5alpha trimerization makes a major contribution to its avidity for the retroviral capsid, and to the ability to restrict virus infection.
Javanbakht
Hassan
H
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, MA 02115, USA.
Yuan
Wen
W
Yeung
Darwin F
DF
Song
Byeongwoon
B
Diaz-Griffero
Felipe
F
Li
Yuan
Y
Li
Xing
X
Stremlau
Matthew
M
Sodroski
Joseph
J
D000090103:Antiviral Restriction Factors; D002213:Capsid / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases