Exploring the structure and function of Thermotoga maritima CorA reveals the mechanism of gating and ion selectivity in Co² /Mg² transport.

NORDIN, Nurhuda; GUSKOV, Albert; PHUA, Terri; SAHAF, Newsha; Yu XIA; Siyan LU; ESHAGHI, Hojjat; ESHAGHI, Said

The CorA family of divalent cation transporters utilizes Mg2 and Co2 as primary substrates. The molecular mechanism of its function, including ion selectivity and gating, has not been fully characterized. Recently we reported a new structure of a CorA homologue from Methanocaldococcus jannaschii, which provided novel structural details that offered the conception of a unique gating mechanism involving conversion of an open hydrophilic gate into a closed hydrophobic one. In the present study we report functional evidence for this novel gating mechanism in the Thermotoga maritima CorA together with an improved crystal structure of this CorA to 2.7 Å (1 Å=0.1 nm) resolution. The latter reveals the organization of the selectivity filter to be similar to that of M. jannaschii CorA and also the previously unknown organization of the second signature motif of the CorA family. The proposed gating is achieved by a helical rotation upon the binding of ametal ion substrate to the regulatory binding sites. Additionally, our data suggest that the preference of this CorA for Co2 over Mg2 is controlled by the presence of threonine side chains in the channel. Finally, the roles of the intracellular metal-binding sites have been assigned to increased thermostability and regulation of the gating. These mechanisms most likely apply to the entire CorA family as they are regulated by the highly conserved amino acids.

ION transport (Biology); METHANOCALDOCOCCUS jannaschii; THERMOTOGA maritima; METAL-binding peptides; MEMBRANE proteins; AMINO acids

Biochemical Journal, 2013, Vol 451, Issue 3, p365

0264-6021

Academic Journal

10.1042/BJ20121745