4y7s

Crystal Structure of the CFEM protein Csa2

spinqualitylabelsall models 4y7s, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4y7s is a 3 chain structure with sequence from Candida albicans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, EDO, HEB Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CSA2_CANAL Secreted heme-binding protein involved in the utilization of iron from human hemoglobin during hyphal growth. May also play a role in non-hemoglobin iron utilization. The ability to acquire iron from host tissues is a major virulence factor of pathogenic microorganisms. Publication Abstract from PubMed Pathogenic microorganisms must cope with extremely low free-iron concentrations in the host's tissues. Some fungal pathogens rely on secreted haemophores that belong to the Common in Fungal Extracellular Membrane (CFEM) protein family, to extract haem from haemoglobin and to transfer it to the cell's interior, where it can serve as a source of iron. Here we report the first three-dimensional structure of a CFEM protein, the haemophore Csa2 secreted by Candida albicans. The CFEM domain adopts a novel helical-basket fold that consists of six alpha-helices, and is uniquely stabilized by four disulfide bonds formed by its eight signature cysteines. The planar haem molecule is bound between a flat hydrophobic platform located on top of the helical basket and a peripheral N-terminal 'handle' extension. Exceptionally, an aspartic residue serves as the CFEM axial ligand, and so confers coordination of Fe(3+) haem, but not of Fe(2+) haem. Histidine substitution mutants of this conserved Asp acquired Fe(2+) haem binding and retained the capacity to extract haem from haemoglobin. However, His-substituted CFEM proteins were not functional in vivo and showed disturbed haem exchange in vitro, which suggests a role for the oxidation-state-specific Asp coordination in haem acquisition by CFEM proteins. Structural basis of haem-iron acquisition by fungal pathogens.,Nasser L, Weissman Z, Pinsky M, Amartely H, Dvir H, Kornitzer D Nat Microbiol. 2016 Sep 12;1:16156. doi: 10.1038/nmicrobiol.2016.156. PMID:27617569 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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