Functional and structural characteristics of bacterial proteins that bind host cytokines

Figures & data

Figure 1. The 3D structures of bacterial cytokine-binding proteins colored from the N-terminus (blue) to the C-terminus (red). (A) The N-terminal PapC domain of Y. pestis Caf1A (PDB:4BOE), the β, N0 and N1 domains of N. meningitidis PilQ (PDB:4AV2), the N-terminal transmembrane domain (PDB:4RLC), and the C-terminal domain (PDB:5U1H) of P. aeruginosa OprF are located in the outer membrane of gram-negative species. (B) E. coli IrmA (PDB:5EK5) and N. meningitidis PilE (PDB:5JW8) are secreted to and face the extracellular space, respectively. The figures were prepared with PyMol (www.pymol.org)

Figure 2. Structural similarities of bacterial cytokine-binding proteins and proteins involved in cytokine signaling. The bacterial proteins are shown in blue. (A) IrmA compared with the N-terminal Ig-fold domain of β-domain of IL-2R (PDB:2B5I), (B) the C-terminal domain of OprF compared with macrophage migration inhibitory factor (MIF) (PDB:4P7M), (C) the N-terminal PapC domain of Caf1A compared with transcription elongation factor b polypeptide 2 (TCEB2) (PDB:2IZV), and (D) the N0 domain of PilQ compared with human granulocyte macrophage colony stimulating factor receptor (GM-CSF) (PDB:5D71) are shown. Superimpositions were performed using the secondary-structure matching (SSM) tool in Coot.⁵⁹ The figures were prepared with PyMol (www.pymol.org)

Table 1. Cytokine-binding bacterial proteins, their ligands and their virulence properties

Protein	Type	Species	Cytokine ligands	Effect of cytokine binding	Virulence	PDB^a	Ref
Caf1A	OM usher	Yp^b	IL-1β	Potential IL-1β uptake	F1 antigen secreted by Caf1A inhibits adhesion to macrophages and airway epithelia, potential vaccine antigen	4BOE (N-terminal PapC domain)	^2,17,23,5-27
PilQ	OM secretin	Nm^c	IL-8, TNF-α	Cytokine uptake, increased virulence, complement resistance	Adherence to nasopharyngeal cells, inhibits phagocytosis by macrophages, initial binding to the blood-brain barrier	4AV2 (Domains N0 and N1)	^6,31,33,34
OprF	OM porin	Pa^d	IFN-γ	Increased production of PA-I lectin and pyocyanin, activation of QS signaling	Adherence to gliad and intestine cells, cytotoxic, induction of other virulence factors, potential vaccine antigen	4RLC (N-terminal transmembrane domain) 5U1H (C-terminal domain)	^5,35,37-40
IrmA	secreted	Ec^e	IL-2, IL-4, IL-10	Not determined	Immunogenic, potential vaccine candidate	5EK5	^7,44
PilE	Pilus subunit	Nm^c	IL-8, TNF-α	Cytokine uptake, increased virulence, complement resistance	Adheres to endothelial cells in the blood-brain barrier, induces host cell signaling	5JW8	^6,45^,^45,47-49
BilRI	OM lipo-protein	Aa^f	IL-1β, IL-8, IL-10, TNF-α, TGF-1β, IFN-γ	IL-1β uptake, decreased amount of extracellular DNA in biofilm	Not determined	N/A	^4,13,42

Notes.

^a The Protein Data Bank

^b Yersinia pestis

^c Neisseria meningitidis

^d Pseudomonas aeruginosa

^e Escherichia coli

^f Aggregatibacter actinomycetemcomitans

Emsley P, Lohkamp B, Scott WG, Cowtan K. Features and development of coot. Acta Crystallogr D Biol Crystallogr. 2010;66:486-501. doi:https://doi.org/10.1107/S0907444910007493. PMID:20383002

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