HIV uses a ‘molecular iris’ to control capsid access

HIV hides its genome inside a proteinaceous shell formed by capsid hexamers to evade detection and degradation in the cytosol of host cells; however, the capsid also hinders access of substrates that are essential for reverse transcription, such as deoxynucleoside triphosphates (dNTPs). Thus far, it was unclear how HIV imported dNTPs into the capsid. Jacques et al. now show that a dynamic pore exists in the centre of each capsid hexamer that enables the entry of dNTPs and thereby supports reverse transcription inside the capsid. The HIV capsid is a conical structure that is formed by a single protein, the capsid protein. Capsid monomers are arranged into a symmetrical hexamer around a central axis and the authors hypothesized that a pore might exist along this axis. However, there was no evidence for such a pore from previous hexamer structures. In fact, previous structures showed that the amino-terminal β-hairpins of each capsid monomer blocked the opening of such a potential pore. When the authors examined this region more closely, including in structures of capsid monomers, they noticed that the β-hairpin is flexible and can assume different conformations by tilting up to 15 Å away from the axis of symmetry. Indeed, when reconstructing a capsid hexamer based on monomer structures with this ‘open’ β-hairpin conformation, a central pore is formed. The conformational change is likely to depend on the protonation status of a histidine residue at the base of the β-hairpin. This is supported by the observation that structures that were obtained at a high crystallisation pH adopted a closed conformation, whereas structures that were obtained at a low pH adopted an open conformation. Interestingly, at physiological pH, the β-hairpin assumes an intermediate position, indicating high flexibility. Thus, the β-hairpin functions as a ‘molecular iris’ that controls entry to a central pore in the capsid. See it on Scoop.it, via Viruses and Bioinformatics from Virology.uvic.ca
HIV uses a 'molecular iris' to control capsid access
Source: Viral Bioinformatics