Crystal structure of Pasteurella haemolytica ferric ion-binding protein A reveals a novel class of bacterial iron-binding proteins.
Pasteurellosis caused by the Gram-negative pathogen Pasteurella haemolytica is a serious disease leading to death in cattle. To scavenge growth-limiting iron from the host, the pathogen utilizes the periplasmic ferric ion-binding protein A (PhFbpA) as a component of an ATP-binding cassette transport pathway. We report the 1.2-A structure of the iron-free (apo) form of PhFbpA, which is a member of the transferrin structural superfamily. The protein structure adopts a closed conformation, allowing us to reliably assign putative iron-coordinating residues. Based on our analysis, PhFbpA utilizes a unique constellation of binding site residues and anions to octahedrally coordinate an iron atom. A surprising finding in the structure is the presence of two formate anions on opposite sides of the iron-binding pocket. The formate ions tether the N- and C-terminal domains of the protein and stabilize the closed structure, also providing clues as to probable candidates for synergistic anions in the iron-loaded state. PhFbpA represents a new class of bacterial iron-binding proteins.
Shouldice
Stephen R
SR
Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
Dougan
Douglas R
DR
Williams
Pamela A
PA
Skene
Robert J
RJ
Snell
Gyorgy
G
Scheibe
Daniel
D
Kirby
Shane
S
Hosfield
David J
DJ
McRee
Duncan E
DE
Schryvers
Anthony B
AB
Tari
Leslie W
LW
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000737:chemistry* / Q000145:classification; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000378:metabolism; D007477:Ions; D007501:Iron / Q000378:metabolism*; D033862:Iron-Binding Proteins; D016978:Mannheimia haemolytica / Q000378:metabolism*; D008958:Models, Molecular; D033902:Periplasmic Binding Proteins; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D014168:Transferrin / Q000737:chemistry / Q000378:metabolism
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D007477:Ions; D033862:Iron-Binding Proteins; D033902:Periplasmic Binding Proteins; D014168:Transferrin; D007501:Iron