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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, RT
Staphylococcus 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 Chemistry

Volume

288

Pagination

1065-1078

ISSN

0021-9258

Department/School

Menzies Institute for Medical Research

Publisher

Amer Soc Biochemistry Molecular Biology Inc

Place of publication

9650 Rockville Pike, Bethesda, USA, Md, 20814-3996

Rights statement

Copyright 2013 The American Society for Biochemistry and Molecular Biology, Inc

Repository Status

  • Restricted

Socio-economic Objectives

Diagnosis of human diseases and conditions

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