Abstract
Cation diffusion facilitator (CDF) proteins are a conserved family of divalent transition metal cation transporters. CDF proteins are usually composed of two domains: the transmembrane domain, in which the metal cations are transported through, and a regulatory cytoplasmic C-terminal domain (CTD). Each CDF protein transports either one specific metal or multiple metals from the cytoplasm, and it is not known whether the CTD takes an active regulatory role in metal recognition and discrimination during cation transport. Here, the model CDF protein MamM, an iron transporter from magnetotactic bacteria, was used to probe the role of the CTD in metal recognition and selectivity. Using a combination of biophysical and structural approaches, the binding of different metals to MamM CTD was characterized. Results reveal that different metals bind distinctively to MamM CTD in terms of their binding sites, thermodynamics, and binding-dependent conformations, both in crystal form and in solution, which suggests a varying level of functional discrimination between CDF domains. Furthermore, these results provide the first direct evidence that CDF CTDs play a role in metal selectivity. We demonstrate that MamM's CTD can discriminate against Mn2+, supporting its postulated role in preventing magnetite formation poisoning in magnetotactic bacteria via Mn2+ incorporation.
Highlights
Cation diffusion facilitator (CDF) proteins are a conserved family of divalent transition metal cation transporters
Crystal structure models of MamM C-terminal domain (CTD) were only obtained in the presence of three different metal cations: Cd21, Ni21, and Cu21
The participation of CDF protein CTDs in metal selectivity was previously studied at the cellular level
Summary
Cation diffusion facilitator (CDF) proteins are a conserved family of divalent transition metal cation transporters. The MamM CTD Cu21-bound structure shows moderate dimerization closure compared with other CDF bound proteins, as was proposed in our previous study of Zn21-binding and associated conformational change in solution [21].
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