Conserved Hinge Motif Modulates Conformational Mobility of a Heme Trafficking Protein from Fusobacterium nucleatum

The structure of the heme-bound HmuF paralog, FldH, reveals an α-helical cap appended to the flavodoxin domain. Molecular dynamics simulations of FldH without heme reveal that the α-helical cap pivots away from the flavodoxin domain to form an open complex, but then reforms the closed complex, which remains closed for the duration of the MD simulation.

Transition to the open conformation disrupts noncovalent interactions formed by three conserved residues (<i>cis</i>-Pro151, His150, and Asp155) that form a hinge bisecting the cap and flavodoxin domain. ¹⁹F NMR was used to probe the dynamics of the cap and the role of the hinge motif. 1D NMR reveals that a single ¹⁹F-Tyr probe in the α-helical cap has two resonances that slowly exchange (τ = 1.5 ms).