Undercovering the interaction of importin 7 and HIV-1 integrase

Karyopherins are a family of nuclear transport receptors responsible for the nucleocytoplasmic transport process in eukaryotic cells. They interact with, and facilitate, the transport of a wide range of macromolecules into the nucleus. Karyopherins can recognize their cargo through nuclear localization signals and nuclear export signals (NLS and NES, respectively). Importin 7 is a karyopherin known to interact with other karyopherins to form a complex facilitating the transport. Importin 7 can take part in the transport not only of eukaryotic macromolecules, but also of viral proteins. In this context, importin 7 is known to promote the transport of one of the human immunodeficiency virus proteins, the HIV-1 integrase. Although the NLS of the HIV-1 integrase is known, their mode of interaction and the transport process are still not clear. In addition, there is no available structure of the complex of importin 7 and HIV-1 integrase. Our goal is to uncover the mechanism of interaction between this karyopherin and its cargo. We preformed several structural studies and carried out biochemical assays in order to decipher the structure and the interactions of the complex of importin 7 and HIV-1 integrase. Here we present the detailed information on the interactions of importin 7 and the NLS of HIV-1 integrase, a revealed via cryo EM with the support of XL-MS. Our results pave a path towards further investigation of this important interaction, with a potential impact on drug design and targeted therapy.