4nla | pdb_00004nla
Structure of the central NEAT domain, N2, of the listerial Hbp2 protein, apo form
Structural highlights
FunctionHBP2_LISMO Acts as an extracellular and cell wall-bound hemophore; scavenges host heme and hemoglobin from the environment and also serves as a cell wall receptor for both (Probable). At low hemin (Hn) and hemoglobin (Hb) concentrations adsorbs Hn/Hb and presumably directs it to membrane transporters (Probable). Soluble Hbp2 can probably pass Hn/Hb to cell wall-anchored Hbp2, and both forms can accept Hn/Hb from Hbp1 (PubMed:25315777). May be involved in crossing the digestive barrier in infected animals (PubMed:15661014). Binds host hemin (Probable) (PubMed:21545655, PubMed:25315777). Binds host hemoglobin with affinity in the nanomolar range (PubMed:25315777).[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedIron is an essential nutrient that is required for the growth of the bacterial pathogen Listeria monocytogenes. In cell cultures, this microbe secretes hemin/hemoglobin-binding protein 2 (Hbp2; Lmo2185) protein, which has been proposed to function as a hemophore that scavenges heme from the environment. Based on its primary sequence, Hbp2 contains three NEAr transporter (NEAT) domains of unknown function. Here we show that each of these domains mediates high affinity binding to ferric heme (hemin) and that its N- and C-terminal domains interact with hemoglobin (Hb). The results of hemin transfer experiments are consistent with Hbp2 functioning as an Hb-binding hemophore that delivers hemin to other Hbp2 proteins that are attached to the cell wall. Surprisingly, our work reveals that the central NEAT domain in Hbp2 binds hemin even though its primary sequence lacks a highly conserved YXXXY motif that is used by all other previously characterized NEAT domains to coordinate iron in the hemin molecule. To elucidate the mechanism of hemin binding by Hbp2, we determined crystal structures of its central NEAT domain (Hbp2(N2); residues 183-303) in its free and hemin-bound states. The structures reveal an unprecedented mechanism of hemin binding in which Hbp2(N2) undergoes a major conformational rearrangement that facilitates metal coordination by a non-canonical tyrosine residue. These studies highlight previously unrecognized plasticity in the hemin binding mechanism of NEAT domains and provide insight into how L. monocytogenes captures heme iron. Novel Mechanism of Hemin Capture by Hbp2, the Hemoglobin-binding Hemophore from Listeria monocytogenes.,Malmirchegini GR, Sjodt M, Shnitkind S, Sawaya MR, Rosinski J, Newton SM, Klebba PE, Clubb RT J Biol Chem. 2014 Dec 12;289(50):34886-99. doi: 10.1074/jbc.M114.583013. Epub, 2014 Oct 14. PMID:25315777[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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