3lhs
Open Conformation of HtsA Complexed with Staphyloferrin AOpen Conformation of HtsA Complexed with Staphyloferrin A
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedStaphylococcus aureus uses several efficient iron acquisition strategies to overcome iron limitation. Recently, the genetic locus encoding biosynthetic enzymes for the iron chelating molecule, staphyloferrin A (SA), was determined. S. aureus synthesizes and secretes SA into its environment to scavenge iron. The membrane-anchored ATP binding cassette-binding protein, HtsA, receives the ferric-chelate for import into the cell. Recently, we determined the apoHtsA crystal structure, the first siderophore receptor from gram-positive bacteria to be structurally characterized. Herein we present the x-ray crystal structure of the HtsA-ferric-SA complex. HtsA adopts a class III binding protein fold composed of separate N- and C-terminal domains bridged by a single alpha-helix. Recombinant HtsA can efficiently sequester ferric-SA from S. aureus culture supernatants where it is bound within the pocket formed between distinct N- and C-terminal domains. A basic patch composed mainly of six Arg residues contact the negatively charged siderophore, securing it within the pocket. The x-ray crystal structures from two different ligand-bound crystal forms were determined. The structures represent the first structural characterization of an endogenous alpha-hydroxycarboxylate-type siderophore-receptor complex. One structure is in an open form similar to apoHtsA, whereas the other is in a more closed conformation. The conformational change is highlighted by isolated movement of three loops within the C-terminal domain, a domain movement unique to known class III binding protein structures. The Staphylococcus aureus siderophore receptor HtsA undergoes localized conformational changes to enclose staphyloferrin A in an arginine-rich binding pocket.,Grigg JC, Cooper JD, Cheung J, Heinrichs DE, Murphy ME J Biol Chem. 2010 Apr 9;285(15):11162-71. Epub 2010 Feb 10. PMID:20147287[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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