title: Why is the GMN motif conserved in the CorA/Mrs2/Alr1 superfamily of magnesium transport proteins?
abstract: Members of the CorA/Mrs2/Alr1 superfamily of transport proteins mediate magnesium uptake in all kingdoms of life. Family members have a low degree of sequence conservation but are characterized by a conserved extracellular loop. While the degree of sequence conservation in the loop deviates to some extent between family members, the GMN family signature motif is always present. Structural and functional data imply that the loop plays a central role in magnesium selectivity, and recent biochemical data suggest it is crucial for stabilizing the pentamer in the magnesium-free (putative open) conformation. In this study, we present a detailed structure-function analysis of the extracellular loop of CorA from Thermotoga maritima, which provides molecular insight into how the loop mediates these two functions. The data show that loop residues outside of the GMN motif can be substituted if they support the pentameric state, but the residues of the GMN motif are intolerant to substitution. We conclude that G(312) is absolutely required for magnesium uptake, M(313) is absolutely required for pentamer integrity in the putative open conformation, and N(314) plays a role in both of these functions. These observations suggest a molecular reason why the GMN motif is conserved throughout the CorA/Mrs2/Alr1 superfamily.
authors.affiliation: Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University , SE-106 91 Stockholm, Sweden.
authors.forename: Isolde
authors.initials: I
authors.lastname: Palombo
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Daley
authors.forename: Mikaela
authors.initials: M
authors.lastname: Rapp
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D027682:Cation Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D017124:Conserved Sequence; D008274:Magnesium / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
chemical_list: D027682:Cation Transport Proteins; D008274:Magnesium