Poster Presentation Society for Molecular Biology and Evolution Conference 2016

Molecular co-evolutionary insights into the HIV-1 pre-integration complex (#584)

Madara Hetti Arachchilage 1 , Helen Piontkivska 1
  1. Kent State University, Kent, OH, United States

The pre-integration complex (PIC), mediated by the viral proteins reverse transcriptase (RT) and integrase (IN), plays an important role in HIV-1 life cycle. The formation and stabilization of the PIC involve direct and indirect interactions between the RT and IN proteins, although the mechanisms of the IN-RT interactions within the PIC remain to be poorly understood due to the transient nature of the protein complex and the intrinsic flexibility of its components. In this study we used the coevolutionary analysis of amino acid sequences of these two proteins to identify potentially interacting regions between the IN and RT proteins within the PIC. Our results enabled us to identify a set of regions with  strong coevolutionary signatures, indicating likely direct and prolonged interactions between them that require high affinity and/or specificity, and hence, higher degree of coevolution. Likewise, such regions may participate in interactions mediated by dynamic conformational changes, including both direct and indirect interactions. Other set of regions was found to have relatively weak, albeit positive correlations, indicating that such regions likely participate in interactions that are transient and/or have low affinity. Overall, for proteins with poorly resolved three-dimensional structures, such as IN, coevolution analysis provides important insights for better understanding of functional interactions and enables identification of specific segments and/or residues involved in interaction interfaces.