Structure and role of the linker domain of the iron surface-determinant protein IsdH in heme transportation in Staphylococcus aureus.
Staphylococcus aureus
heme
heme acquisition
heme transport
hemoglobin
hemoglobin receptor
hydrogen exchange mass spectrometry
iron surface determinant system
structure-function
x-ray crystallography
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
28
12
2021
revised:
25
04
2022
accepted:
26
04
2022
pubmed:
3
5
2022
medline:
30
6
2022
entrez:
2
5
2022
Statut:
ppublish
Résumé
Staphylococcus aureus is a major cause of deadly nosocomial infections, a severe problem fueled by the steady increase of resistant bacteria. The iron surface determinant (Isd) system is a family of proteins that acquire nutritional iron from the host organism, helping the bacterium to proliferate during infection, and therefore represents a promising antibacterial target. In particular, the surface protein IsdH captures hemoglobin (Hb) and acquires the heme moiety containing the iron atom. Structurally, IsdH comprises three distinctive NEAr-iron Transporter (NEAT) domains connected by linker domains. The objective of this study was to characterize the linker region between NEAT2 and NEAT3 from various biophysical viewpoints and thereby advance our understanding of its role in the molecular mechanism of heme extraction. We demonstrate the linker region contributes to the stability of the bound protein, likely influencing the flexibility and orientation of the NEAT3 domain in its interaction with Hb, but only exerts a modest contribution to the affinity of IsdH for heme. Based on these data, we suggest that the flexible nature of the linker facilitates the precise positioning of NEAT3 to acquire heme. In addition, we also found that residues His45 and His89 of Hb located in the heme transfer route toward IsdH do not play a critical role in the transfer rate-determining step. In conclusion, this study clarifies key elements of the mechanism of heme extraction of human Hb by IsdH, providing key insights into the Isd system and other protein systems containing NEAT domains.
Identifiants
pubmed: 35500652
pii: S0021-9258(22)00435-5
doi: 10.1016/j.jbc.2022.101995
pmc: PMC9163592
pii:
doi:
Substances chimiques
Antigens, Bacterial
0
Hemoglobins
0
IsdH protein, Staphylococcus aureus
0
Membrane Proteins
0
Receptors, Cell Surface
0
Heme
42VZT0U6YR
Iron
E1UOL152H7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
101995Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interests The authors declare no conflict of interest.
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