NMR experiments redefine the hemoglobin binding properties of bacterial NEAr‐iron Transporter domains

Iron is a versatile metal cofactor that is used in a wide range of essential cellular processes. During infections, many bacterial pathogens acquire iron from human hemoglobin (Hb), which contains the majority of the body's total iron content in the form of heme (iron protoporphyrin IX). Clinic...

Full description

Saved in:
Bibliographic Details
Published in:Protein science 2019-08, Vol.28 (8), p.1513-1523
Main Authors: Macdonald, Ramsay, Mahoney, Brendan J., Ellis‐Guardiola, Ken, Maresso, Anthony, Clubb, Robert T.
Format: Article
Language:English
Subjects:
Bacteria
Binding
For the Record
Heme
Hemoglobin
Iron
Listeria
Listeria monocytogenes
Magnetic resonance spectroscopy
NEAT domain
NMR
NMR spectroscopy
Nuclear magnetic resonance
pathogen
Pathogens
Properties (attributes)
Protoporphyrin
Protoporphyrin IX
Receptors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Iron is a versatile metal cofactor that is used in a wide range of essential cellular processes. During infections, many bacterial pathogens acquire iron from human hemoglobin (Hb), which contains the majority of the body's total iron content in the form of heme (iron protoporphyrin IX). Clinically important Gram‐positive bacterial pathogens scavenge heme using an array of secreted and cell‐wall‐associated receptors that contain NEAr‐iron Transporter (NEAT) domains. Experimentally defining the Hb binding properties of NEAT domains has been challenging, limiting our understanding of their function in heme uptake. Here we show that solution‐state NMR spectroscopy is a powerful tool to define the Hb binding properties of NEAT domains. The utility of this method is demonstrated using the NEAT domains from Bacillus anthracis and Listeria monocytogenes. Our results are compatible with the existence of at least two types of NEAT domains that are capable of interacting with either Hb or heme. These binding properties can be predicted from their primary sequences, with Hb‐ and heme‐binding NEAT domains being distinguished by the presence of (F/Y)YH(Y/F) and S/YXXXY motifs, respectively. The results of this work should enable the functions of a wide range of NEAT domain containing proteins in pathogenic bacteria to be reliably predicted.
ISSN:0961-8368
1469-896X
DOI:10.1002/pro.3662