Structural biology of heme binding in the Staphylococcus aureus Isd system.
Iron is an absolute requirement for nearly all organisms, but most bacterial pathogens are faced with extreme iron-restriction within their host environments. To overcome iron limitation pathogens have evolved precise mechanisms to steal iron from host supplies. Staphylococcus aureus employs the iron-responsive surface determinant (Isd) system as its primary heme-iron uptake pathway. Hemoglobin or hemoglobin-haptoglobin complexes are bound by Near iron-Transport (NEAT) domains within cell surface anchored proteins IsdB or IsdH. Heme is stripped from the host proteins and transferred between NEAT domains through IsdA and IsdC to the membrane transporter IsdEF for internalization. Once internalized, heme can be degraded by IsdG or IsdI, thereby liberating iron for the organism. Most components of the Isd system have been structurally characterized to provide insight into the mechanisms of heme binding and transport. This review summarizes recent research on the Isd system with a focus on the structural biology of heme recognition.
Grigg
Jason C
JC
Department of Microbiology and Immunology, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada V6T1Z4.
Ukpabi
Georgia
G
Gaudin
Catherine F M
CF
Murphy
Michael E P
ME
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D002473:Cell Wall / Q000378:metabolism; D018360:Crystallography, X-Ray; D006242:Haptoglobins / Q000378:metabolism; D006418:Heme / Q000737:chemistry / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011485:Protein Binding; D011487:Protein Conformation; D016415:Sequence Alignment; D013211:Staphylococcus aureus / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity
D001426:Bacterial Proteins; D006242:Haptoglobins; D006454:Hemoglobins; C035492:haptoglobin-hemoglobin complex; D006418:Heme; D007501:Iron