The structure of the BfrB-Bfd complex reveals protein-protein interactions enabling iron release from bacterioferritin.
Ferritin-like molecules are unique to cellular iron homeostasis because they can store iron at concentrations much higher than those dictated by the solubility of Fe(3+). Very little is known about the protein interactions that deliver iron for storage or promote the mobilization of stored iron from ferritin-like molecules. Here, we report the X-ray crystal structure of Pseudomonas aeruginosa bacterioferritin (Pa-BfrB) in complex with bacterioferritin-associated ferredoxin (Pa-Bfd) at 2.0 Å resolution. As the first example of a ferritin-like molecule in complex with a cognate partner, the structure provides unprecedented insight into the complementary interface that enables the [2Fe-2S] cluster of Pa-Bfd to promote heme-mediated electron transfer through the BfrB protein dielectric (~18 Å), a process that is necessary to reduce the core ferric mineral and facilitate mobilization of Fe(2+). The Pa-BfrB-Bfd complex also revealed the first structure of a Bfd, thus providing a first view to what appears to be a versatile metal binding domain ubiquitous to the large Fer2_BFD family of proteins and enzymes with diverse functions. Residues at the Pa-BfrB-Bfd interface are highly conserved in Bfr and Bfd sequences from a number of pathogenic bacteria, suggesting that the specific recognition between Pa-BfrB and Pa-Bfd is of widespread significance to the understanding of bacterial iron homeostasis.
Department of Chemistry, University of Kansas, Multidisciplinary Research Building, 2030 Becker Drive, Lawrence, Kansas 66047, USA.
Huili
H
Yao
Yan
Y
Wang
Scott
S
Lovell
Ritesh
R
Kumar
Anatoly M
AM
Ruvinsky
Kevin P
KP
Battaile
Ilya A
IA
Vakser
Mario
M
Rivera
D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D003573:Cytochrome b Group / Q000737:chemistry* / Q000378:metabolism*; D005288:Ferredoxins / Q000737:chemistry* / Q000378:metabolism; D005293:Ferritins / Q000737:chemistry* / Q000378:metabolism*; D007501:Iron / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D017510:Protein Folding; D011550:Pseudomonas aeruginosa / Q000378:metabolism
D001426:Bacterial Proteins; D003573:Cytochrome b Group; D005288:Ferredoxins; D005293:Ferritins; C018032:bacterioferritin; D007501:Iron