The Staphylococcus aureus IsdH Receptor Forms a Dynamic Complex with Human Hemoglobin that Triggers Heme Release via Two Distinct Hot Spots.

ABSTRACT: Iron is an essential nutrient that is actively acquired by bacterial pathogens during infections. Clinically important Staphylococcus aureus obtains iron by extracting heme from hemoglobin (Hb) using the closely related IsdB and IsdH surface receptors. In IsdH, extraction is mediated by a conserved tridomain unit that contains its second (N2) and third (N3) NEAT domains joined by a helical linker, called IsdH^N2N3. Leveraging the crystal structure of the IsdH^N2N3:Hb complex, we have probed the mechanism of heme capture using NMR, stopped-flow transfer kinetics measurements, and molecular dynamics (MD) simulations. NMR studies of the 220 kDa IsdH^N2N3:Hb complex reveal that it is dynamic, with persistent interdomain motions enabling the linker and N3 domains i

SUBMITTER: Ellis-Guardiola K 

PROVIDER: S-EPMC7309296 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature