Structural asymmetry in the magnesium channel CorA points to sequential allosteric regulation

Proc Natl Acad Sci U S A. 2012 Nov 13;109(46):18809-14. doi: 10.1073/pnas.1209018109. Epub 2012 Oct 29.


Magnesium ions (Mg(2+)) are essential for life, but the mechanisms regulating their transport into and out of cells remain poorly understood. The CorA-Mrs2-Alr1 superfamily of Mg(2+) channels represents the most prevalent group of proteins enabling Mg(2+) ions to cross membranes. Thermotoga maritima CorA (TmCorA) is the only member of this protein family whose complete 3D fold is known. Here, we report the crystal structure of a mutant in the presence and absence of divalent ions and compare it with previous divalent ion-bound TmCorA structures. With Mg(2+) present, this structure shows binding of a hydrated Mg(2+) ion to the periplasmic Gly-Met-Asn (GMN) motif, revealing clues of ion selectivity in this unique channel family. In the absence of Mg(2+), TmCorA displays an unexpected asymmetric conformation caused by radial and lateral tilts of protomers that leads to bending of the central, pore-lining helix. Molecular dynamics simulations support these movements, including a bell-like deflection. Mass spectrometric analysis confirms that major proteolytic cleavage occurs within a region that is selectively exposed by such a bell-like bending motion. Our results point to a sequential allosteric model of regulation, where intracellular Mg(2+) binding locks TmCorA in a symmetric, transport-incompetent conformation and loss of intracellular Mg(2+) causes an asymmetric, potentially influx-competent conformation of the channel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Cation Transport Proteins / chemistry*
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism
  • Crystallography, X-Ray
  • Magnesium / chemistry*
  • Magnesium / metabolism
  • Molecular Dynamics Simulation*
  • Protein Structure, Tertiary
  • Structure-Activity Relationship
  • Thermotoga maritima / chemistry*
  • Thermotoga maritima / genetics
  • Thermotoga maritima / metabolism


  • Bacterial Proteins
  • Cation Transport Proteins
  • Magnesium

Associated data

  • PDB/4EEB
  • PDB/4EED