Structural and dynamic insights into Mn4Ca cluster-depleted Photosystem II

In the first steps of natural oxygenic photosynthesis, Sun light is used to oxidize water molecules into protons, electrons and molecular oxygen. This reaction takes place on the Mn$_4$Ca cluster located in the reaction centre of Photosystem II (PSII), where the cluster is assembled and continuously repaired through a process known as photoactivation. Understanding the molecular details of such process has important implications in different fields, in particular inspiring synthesis and repair strategies for artificial photosynthesis devices. In this regard, a detailed structural and dynamic characterization of the Photosystem II lacking Mn$_4$Ca cluster, namely $apo$ PSII, is a prerequisite for the full comprehension of the photoactivation. Recently, the structure of the $apo$ PSII was resolved at 2.55~\AA~resolution [Zhang \textit{et al., eLIFE}, 2017, \textbf{6}, e26933], suggesting a pre-organized structure of the protein cavity hosting the cluster. Anyway, the question whether these findings are a feature of the method used remains open. Here, by means of classical Molecular Dynamics simulations, we characterized structural and dynamic features of the $apo$ PSII for different protonation states of the cluster cavity. Albeit an overall conformational stability common to all investigated systems, we found significant deviations in the conformation of the side chains of the active site with respect to the x-ray positions. Our findings suggest that not all residues acting as Mn ligands are pre-organized prior the Mn$_4$Ca formation and previous local conformational changes are required in order to bind the first Mn ion in the high-affinity binding site.