Structural highlights
Function
[ISDA_STAAW] Transfers its hemin to hemin-free IsdC (apo-IsdC) directly probably through the activated holo-IsdA-apo-IsdC complex and driven by the higher affinity of apo-IsdC for the cofactor. The reaction is reversible. Binds transferrin, lactoferrin, heme, hemoglobin, hemin, fetuin, asialofetuin and protein A. Also binds fibronectin and chains B-beta and gamma of fibrinogen. Could play a role in the removal of heme from hemoglobin. The IsdA-mediated iron-acquisition system from transferrin could play only an ancillary role in the iron uptake whereas the siderophore-mediated iron-acquisition system from transferrin seems to play an essential or dominant role. May function as a reservoir for heme. Involved in adherence of S.aureus to human desquamated nasal epithelial cells and is required for nasal colonization. Protects S.aureus against the bactericidal protease activity of apolactoferrin in vitro and confers resistance to bovine lactoferricin (By similarity). Also IsdA and/or IsdB promote resistance to hydrogen peroxide and killing by neutrophils.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Successful pathogenic organisms have developed mechanisms to thrive under extreme levels of iron restriction. Haem-iron represents the largest iron reservoir in the human body and is a significant source of iron for some bacterial pathogens. NEAT (NEAr Transporter) domains are found exclusively in a family of cell surface proteins in Gram-positive bacteria. Many NEAT domain-containing proteins, including IsdA in Staphylococcus aureus, are implicated in haem binding. Here, we show that overexpression of IsdA in S. aureus enhances growth and an inactivation mutant of IsdA has a growth defect, compared with wild type, when grown in media containing haem as the sole iron source. Furthermore, the haem-binding property of IsdA is contained within the NEAT domain. Crystal structures of the apo-IsdA NEAT domain and in complex with haem were solved and reveal a clathrin adapter-like beta-sandwich fold with a large hydrophobic haem-binding pocket. Haem is bound with the propionate groups directed at the molecular surface and the iron is co-ordinated solely by Tyr(166). The phenol groups of Tyr(166) and Tyr(170) form an H-bond that may function in regulating haem binding and release. An analysis of IsdA structure-sequence alignments indicate that conservation of Tyr(166) is a predictor of haem binding by NEAT domains.
Haem recognition by a Staphylococcus aureus NEAT domain.,Grigg JC, Vermeiren CL, Heinrichs DE, Murphy ME Mol Microbiol. 2007 Jan;63(1):139-49. PMID:17229211[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Palazzolo-Ballance AM, Reniere ML, Braughton KR, Sturdevant DE, Otto M, Kreiswirth BN, Skaar EP, DeLeo FR. Neutrophil microbicides induce a pathogen survival response in community-associated methicillin-resistant Staphylococcus aureus. J Immunol. 2008 Jan 1;180(1):500-9. PMID:18097052
- ↑ Liu M, Tanaka WN, Zhu H, Xie G, Dooley DM, Lei B. Direct hemin transfer from IsdA to IsdC in the iron-regulated surface determinant (Isd) heme acquisition system of Staphylococcus aureus. J Biol Chem. 2008 Mar 14;283(11):6668-76. doi: 10.1074/jbc.M708372200. Epub 2008 , Jan 9. PMID:18184657 doi:http://dx.doi.org/10.1074/jbc.M708372200
- ↑ Grigg JC, Vermeiren CL, Heinrichs DE, Murphy ME. Haem recognition by a Staphylococcus aureus NEAT domain. Mol Microbiol. 2007 Jan;63(1):139-49. PMID:17229211 doi:10.1111/j.1365-2958.2006.05502.x
