Structure and transport mechanism of human riboflavin transporters

Riboflavin (vitamin B2) is the precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which act as key cofactors of many enzymes, thus has essential roles in cell growth and functions. Animals cannot synthesize riboflavin in situ, the intake, distribution and metabolism of which are mediated by three riboflavin transporters (RFVT1-3). Many mutations in RFVTs cause severe consequences. How RFVTs recognize and transport riboflavin remains largely unknown. On the basis of cryo-electron microscopy structures of human RFVT2 and RFVT3 in complex with riboflavin, we conducted MD simulations on four systems, including RFVT2 with or without riboflavin bound and RFVT3 with or without riboflavin bound.