Structural analysis of ABC-family periplasmic zinc binding protein provides new insights into mechanism of ligand uptake and release

J Mol Biol. 2007 Apr 6;367(4):970-82. doi: 10.1016/j.jmb.2007.01.041. Epub 2007 Jan 23.

Abstract

ATP-binding cassette superfamily of periplasmic metal transporters are known to be vital for maintaining ion homeostasis in several pathogenic and non-pathogenic bacteria. We have determined crystal structure of the high-affinity zinc transporter ZnuA from Escherichia coli at 1.8 A resolution. This structure represents the first native (non-recombinant) protein structure of a periplasmic metal binding protein. ZnuA reveals numerous conformational features, which occur either in Zn(2+) or in Mn(2+) transporters, and presents a unique conformational state. A comprehensive comparison of ZnuA with other periplasmic ligand binding protein structures suggests vital mechanistic differences between bound and release states of metal transporters. The key new attributes in ZnuA include a C-domain disulfide bond, an extra alpha-helix proximal to the highly charged metal chelating mobile loop region, alternate conformations of secondary shell stabilizing residues at the metal binding site, and domain movements potentially controlled by salt bridges. Based on in-depth structural analyses of five metal binding transporters, we present here a mechanistic model termed as "partial domain slippage" for binding and release of Zn(2+).

Publication types

  • Comparative Study

MeSH terms

  • ATP-Binding Cassette Transporters / chemistry*
  • ATP-Binding Cassette Transporters / metabolism
  • Amino Acid Sequence
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism
  • Crystallography, X-Ray
  • Escherichia coli
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / metabolism
  • Hydrogen Bonding
  • Models, Biological
  • Models, Molecular
  • Molecular Sequence Data
  • Periplasmic Binding Proteins / chemistry
  • Periplasmic Binding Proteins / metabolism
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Sulfhydryl Compounds / chemistry
  • Zinc / metabolism*

Substances

  • ATP-Binding Cassette Transporters
  • Carrier Proteins
  • Escherichia coli Proteins
  • Periplasmic Binding Proteins
  • Sulfhydryl Compounds
  • ZnuA protein, E coli
  • zinc-binding protein
  • Zinc

Associated data

  • PDB/2OGW