Mg(2+)-dependent gating of bacterial MgtE channel underlies Mg(2+) homeostasis.
The MgtE family of Mg(2+) transporters is ubiquitously distributed in all phylogenetic domains. Recent crystal structures of the full-length MgtE and of its cytosolic domain in the presence and absence of Mg(2+) suggested a Mg(2+)-homeostasis mechanism, in which the MgtE cytosolic domain acts as a 'Mg(2+) sensor' to regulate the gating of the ion-conducting pore in response to the intracellular Mg(2+) concentration. However, complementary functional analyses to confirm the proposed model have been lacking. Moreover, the limited resolution of the full-length structure precluded an unambiguous characterization of these regulatory divalent-cation-binding sites. Here, we showed that MgtE is a highly Mg(2+)-selective channel gated by Mg(2+) and elucidated the Mg(2+)-dependent gating mechanism of MgtE, using X-ray crystallographic, genetic, biochemical, and electrophysiological analyses. These structural and functional results have clarified the control of Mg(2+) homeostasis through cooperative Mg(2+) binding to the MgtE cytosolic domain.
Department of Basic Medical Sciences, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
Motoyuki
M
Hattori
Norihiko
N
Iwase
Noritaka
N
Furuya
Yoshiki
Y
Tanaka
Tomoya
T
Tsukazaki
Ryuichiro
R
Ishitani
Michael E
ME
Maguire
Koichi
K
Ito
Andres
A
Maturana
Osamu
O
Nureki
D017920:Antiporters / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D018407:Bacterial Physiological Phenomena; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D006706:Homeostasis / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology*; D008274:Magnesium / Q000378:metabolism* / Q000502:physiology; D008954:Models, Biological; D008958:Models, Molecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary / Q000502:physiology; D013379:Substrate Specificity; D016963:Thermus thermophilus / Q000737:chemistry / Q000378:metabolism
D017920:Antiporters; D001426:Bacterial Proteins; C092192:MgtE protein, bacteria; D008274:Magnesium