Molecular mechanism of Mg2+-dependent gating in CorA.
CorA is the major transport system responsible for Mg(2+) uptake in bacteria and can functionally substitute for its homologue Mrs2p in the yeast inner mitochondrial membrane. Although several CorA crystal structures are available, the molecular mechanism of Mg(2+) uptake remains to be established. Here we use electron paramagnetic resonance spectroscopy, electrophysiology and molecular dynamic simulations to show that CorA is regulated by cytoplasmic Mg(2+) acting as a ligand and elucidate the basic conformational rearrangements responsible for Mg(2+)-dependent gating. Mg(2+) unbinding at the divalent cation sensor triggers a conformational change that leads to the inward motion of the stalk helix, which propagates to the pore-forming transmembrane helix TM1. Helical tilting and rotation in TM1 generates an iris-like motion that increases the diameter of the permeation pathway, triggering ion conduction. This work establishes the molecular basis of a Mg(2+)-driven negative feedback loop in CorA as the key physiological event controlling Mg(2+) uptake and homeostasis in prokaryotes.
Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago, 929 E. 57th Street, Chicago, Illinois 60637, USA.
Olivier
O
Dalmas
Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
Pornthep
P
Sompornpisut
Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago, 929 E. 57th Street, Chicago, Illinois 60637, USA.
Francisco
F
Bezanilla
Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago, 929 E. 57th Street, Chicago, Illinois 60637, USA.
Eduardo
E
Perozo
D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D027682:Cation Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D007477:Ions / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism*; D017433:Protein Structure, Secondary; D020124:Thermotoga maritima / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D001426:Bacterial Proteins; D027682:Cation Transport Proteins; D007477:Ions; D008274:Magnesium