Molecular Basis for Vacuolar Iron Transport by OsVIT2, a Target for Iron Biofortification in Rice.

Iron deficiency is the prevalent and most widespread nutritional shortfall for humans, affecting over 30% of the global population and leading to anemia, particularly among preschool-aged children and pregnant women in developing countries. Simultaneously, while half of the world's population depends on rice (Oryza sativa L.) as a staple food, this cereal does not provide a sufficient amount of that micronutrient to meet these people's nutritional needs: even when iron is readily available in the soil, it does not accumulate in the consumed portion of the grain, namely, the starchy endosperm, being instead retained in the aleurone layer, in the pericarp and in the embryo. In this context, the present work applies computational biology tools-such as normal mode analysis and molecular dynamics simulations-to elucidate the behavior and transport mechanism of the Vacuolar Iron Transporter 2 (OsVIT2), a central protein for iron homeostasis in rice, with the objective of laying the foundations for future OsVIT2 engineering projects that could be articulated with ongoing efforts to promote iron biofortification in rice. We shed light on the interplay between protonation state, configuration and hydration of OsVIT2's pore; on the mechanics of its opening and on the ever-shifting hydrogen bond network contained within it. We also explore the potential contribution of the "flexible arms" to the iron-capturing function performed by the cytoplasmic domain.