2O6P

Crystal Structure of the heme-IsdC complex

Summary for 2O6P

• Entry DOI: 10.2210/pdb2o6p/pdb
• Descriptor: Iron-regulated surface determinant protein C, ZINC ION, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: beta barrel, protein-heme complex, transport protein
• Biological source: Staphylococcus aureus subsp. aureus
• Cellular location: Secreted, cell wall ; Peptidoglycan-anchor : Q7A654
• Total number of polymer chains: 2
• Total formula weight: 37319.04

Authors

Sharp, K.H.,Schneider, S.,Cockayne, A.,Paoli, M. (deposition date: 2006-12-08, release date: 2007-02-06, Last modification date: 2023-12-27)

Primary citation

Sharp, K.H.,Schneider, S.,Cockayne, A.,Paoli, M.
Crystal structure of the heme-IsdC complex, the central conduit of the Isd iron/heme uptake system in Staphylococcus aureus.
J. Biol. Chem., 282:10625-10631, 2007

PubMed Abstract: Pathogens such as Staphylococcus aureus require iron to survive and have evolved specialized proteins to steal heme from their host. IsdC is the central conduit of the Isd (iron-regulated surface determinant) multicomponent heme uptake machinery; staphylococcal cell-surface proteins such as IsdA, IsdB, and IsdH are thought to funnel their molecular cargo to IsdC, which then mediates the transfer of the iron-containing nutrient to the membrane translocation system IsdDEF. The structure of the heme-IsdC complex reveals a novel heme site within an immunoglobulin-like domain and sheds light on its binding mechanism. The folding topology is reminiscent of the architecture of cytochrome f, cellobiose dehydrogenase, and ethylbenzene dehydrogenase; in these three proteins, the heme is bound in an equivalent position, but interestingly, IsdC features a distinct binding pocket with the ligand located next to the hydrophobic core of the beta-sandwich. The iron is coordinated with a tyrosine surrounded by several non-polar side chains that cluster into a tightly packed proximal side. On the other hand, the distal side is relatively exposed with a short helical peptide segment that acts as a lip clasping onto almost half of the porphyrin plane. This structural feature is argued to play a role in the mechanism of binding and release by switching to an open conformation and thus loosening the interactions holding the heme. The structure of the heme-IsdC complex provides a template for the understanding of other proteins, such as IsdA, IsdB, and IsdH, that contain the same heme-binding module as IsdC, known as the NEAT (near transporter) domain.

PubMed: 17287214
DOI: 10.1074/jbc.M700234200

Experimental method

X-RAY DIFFRACTION (1.5 Å)