Role of I182, R187 and K188 Amino Acids of the Catalytic Domain of HIV-1 Integrase in the Processes of Reverse Transcription and Integration

The structural organization of HIV-1 integrase is based on a tetramer formed by two protein dimers. Within this tetramer, the catalytic domain of one subunit of the first dimer interacts with the N-terminal domain of a subunit of the second dimer. It is the tetrameric structure that allows both ends of viral DNA to be correctly positioned relative to cellular DNA and to implement the catalytic functions of integrase, namely 3′-processing and strand transfer. However, during the HIV-1 replicative cycle, integrase is responsible not only for the integration stage, it is also involved in reverse transcription and is necessary at the stage of capsid formation of newly formed virions. HIV-1 integrase is proposed to be a structurally dynamic protein and its biological functions depend on its structure. Accordingly, studying the interactions between the domains of integrase that provide its tetrameric structure is important for understanding its multiple functions. In this work, we investigated the role of three amino acids of the catalytic domain I182, R187 and K188, located in the contact region of two integrase dimers in the tetramer structure, in reverse transcription and integration. It has been shown that the R187 residue is extremely important for the formation of the correct integrase structure, which is necessary at all stages of its functional activity. The I182 residue is necessary for successful integration and is not important for reverse transcription, while the K188 residue, on the contrary, is involved in the formation of the integrase structure, which is important for effective reverse transcription.