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Staphylococcus aureus uses a novel multidomain receptor to break apart human hemoglobin and steal its heme
journal contribution
posted on 2023-05-17, 17:38 authored by Spirig, T, Malmirchegini, GR, Zhang, J, Robson, SA, Sjodt, M, Liu, M, Kumar, KK, Dickson, CF, David GellDavid Gell, Lei, B, Loo, JA, Clubb, RTStaphylococcus aureus is a leading cause of life-threatening infections in the United States. It requires iron to grow, which must be actively procured from its host to successfully mount an infection. Heme-iron within hemoglobin (Hb) is the most abundant source of iron in the human body and is captured by S. aureus using two closely related receptors, IsdH and IsdB. Here we demonstrate that each receptor captures heme using two conserved near iron transporter (NEAT) domains that function synergistically. NMR studies of the 39-kDa conserved unit from IsdH (IsdHN2N3, Ala326-Asp660) reveals that it adopts an elongated dumbbell-shaped structure in which its NEAT domains are properly positioned by a helical linker domain, whose three-dimensional structure is determined here in detail. Electrospray ionization mass spectrometry and heme transfer measurements indicate that IsdHN2N3 extracts heme from Hb via an ordered process in which the receptor promotes heme release by inducing steric strain that dissociates the Hb tetramer. Other clinically significant Gram-positive pathogens capture Hb using receptors that contain multiple NEAT domains, suggesting that they use a conserved mechanism. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.
History
Publication title
Journal of Biological ChemistryVolume
288Pagination
1065-1078ISSN
0021-9258Department/School
Menzies Institute for Medical ResearchPublisher
Amer Soc Biochemistry Molecular Biology IncPlace of publication
9650 Rockville Pike, Bethesda, USA, Md, 20814-3996Rights statement
Copyright 2013 The American Society for Biochemistry and Molecular Biology, IncRepository Status
- Restricted
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