Hijacking transferrin bound iron: protein-receptor interactions involved in iron transport in N. gonorrhoeae.
Neisseria gonorrhoeae has the capacity to acquire iron from its human host by removing this essential nutrient from serum transferrin. The transferrin binding proteins, TbpA and TbpB constitute the outer membrane receptor complex responsible for binding transferrin, extracting the tightly bound iron from the host-derived molecule, and transporting iron into the periplasmic space of this Gram-negative bacterium. Once iron is transported across the outer membrane, ferric binding protein A (FbpA) moves the iron across the periplasmic space and initiates the process of transport into the bacterial cytosol. The results of the studies reported here define the multiple steps in the iron transport process in which TbpA and TbpB participate. Using the SUPREX technique for assessing the thermodynamic stability of protein-ligand complexes, we report herein the first direct measurement of periplasmic FbpA binding to the outer membrane protein TbpA. We also show that TbpA discriminates between apo- and holo-FbpA; i.e. the TbpA interaction with apo-FbpA is higher affinity than the TbpA interaction with holo-FbpA. Further, we demonstrate that both TbpA and TbpB individually can deferrate transferrin and ferrate FbpA without energy supplied from TonB resulting in sequestration by apo-FbpA.
Siburt
Claire J Parker
CJ
Department of Chemistry, Duke University, Durham, NC 27708-0346, USA.
Roulhac
Petra L
PL
Weaver
Katherine D
KD
Noto
Jennifer M
JM
Mietzner
Timothy A
TA
Cornelissen
Cynthia N
CN
Fitzgerald
Michael C
MC
Crumbliss
Alvin L
AL
D006801:Humans; D007501:Iron / Q000737:chemistry / Q000378:metabolism*; D009344:Neisseria gonorrhoeae / Q000737:chemistry / Q000378:metabolism*; D014168:Transferrin / Q000737:chemistry / Q000378:metabolism*; D033881:Transferrin-Binding Protein A / Q000737:chemistry / Q000378:metabolism*; D033882:Transferrin-Binding Protein B / Q000737:chemistry / Q000378:metabolism*
D014168:Transferrin; D033881:Transferrin-Binding Protein A; D033882:Transferrin-Binding Protein B; D007501:Iron