3LHS

Open Conformation of HtsA Complexed with Staphyloferrin A

Summary for 3LHS

• Entry DOI: 10.2210/pdb3lhs/pdb
• Related: 3eiw 3eix 3LI2
• Descriptor: Ferrichrome ABC transporter lipoprotein, GLYCEROL, FE (III) ION, ... (5 entities in total)
• Functional Keywords: siderophore, iron, receptor, lipoprotein, binding protein, transport protein
• Biological source: Staphylococcus aureus subsp. aureus strain
• Total number of polymer chains: 1
• Total formula weight: 34171.90

Authors

Grigg, J.C.,Murphy, M.E.P. (deposition date: 2010-01-23, release date: 2010-02-09, Last modification date: 2024-02-21)

Primary citation

Grigg, J.C.,Cooper, J.D.,Cheung, J.,Heinrichs, D.E.,Murphy, M.E.
The Staphylococcus aureus siderophore receptor HtsA undergoes localized conformational changes to enclose staphyloferrin A in an arginine-rich binding pocket.
J.Biol.Chem., 285:11162-11171, 2010

PubMed Abstract: Staphylococcus 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.

PubMed: 20147287
DOI: 10.1074/jbc.M109.097865

Experimental method

X-RAY DIFFRACTION (1.3 Å)