Molecular models of heme transfer in C. diphtheriae.

Abstract

Corynebacterium diphtheriae is a bacteria that uses iron to assist in its survival and proliferation. It commonly obtains iron from host hemoglobin or the hemoglobin-haptoglobin complex. The protein pathway of the heme transport contains multiple proteins, including HbpA, ChtA, HtaA, HtaB, and HmuT, and the heme is shuttled between these proteins through a process that likely involves the formation of multiple transient protein/protein interfaces. However, the molecular mechanisms underlying heme acquisition and transport in these multimeric complexes remains unknown. To better understand these iron acquisition dynamics, we have performed a series of molecular dynamic (MD) simulations along the C. diphtheriae heme transfer pathway starting from unique rigid body docking structures, and used them to produce Markov State Models that reveal the kinetics and thermodynamics of the protein/protein association complexes. Results show a dynamic protein interface reveals intricacies of the heme acquisition process on the microsecond timescale.