GTP activator and dNTP substrates of HIV-1 restriction factor SAMHD1 generate a long-lived activated state
Abstract
The degradative dNTP triphosphohydrolase activity of the sterile α-motif/histidine-aspartate domain-containing protein 1 (SAMHD1) enzyme helps maintain optimal dNTP balances for DNA replication and also serves as an HIV-1 restriction factor in resting CD4+ target cells of HIV by depleting dNTP substrates of reverse transcriptase. This study shows that full activation of SAMHD1 involves ordered binding of GTP and substrate dNTPs to activator and substrate sites on the enzyme, leading to ordered assembly of the tetramer active form. After the enzyme is activated, it no longer communicates with free activator nucleotides, which contributes to efficient depletion of dNTP pools in resting T cells.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- May 2014
- DOI:
- 10.1073/pnas.1401706111
- Bibcode:
- 2014PNAS..111E1843H