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Background
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The redox state of cysteine-rich region of HIV tat protein is known to play a crucial role in tat biological activity. The cysteine-rich region, encompassing seven cysteine residues, is highly conserved among the different HIV-1 strains and isolates. Its redox state is known to be important for protein function and activity. In particular, variation of the tat cysteine motif known as "cysteine 30-cysteine 31" (C30C31) is associated with clade-specific tat neurotoxicity. Formation of tat homodimers also depends on the oxidation state of the protein, as dimerization requires metal ions binding to free sulphydryl groups present in the cysteine region. In the presence of oxygen and in absence of reducing agents, tat protein rapidly oxidises forming intra-molecular disulfide bonds which prevent the interaction with metal ions. Further, oxidation induces the formation of inter-molecular disulfide bonds causing tat multimerization and aggregation. Due to these effects, oxidation hampers or abrogates tat biological activity.
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