Journal:JBIC:14

SlyD belongs to the FK506-binding protein (FKBP) family with both peptidylprolyl isomerase (PPIase) and chaperone activities, and is considered to be a ubiquitous cytosolic protein-folding facilitator in bacteria. It possesses a histidine- and cysteine-rich C-terminus binding to selected divalent metal ions (e.g., Ni²⁺, Zn²⁺), which is important for its involvement in the maturation processes of metalloenzymes. We have determined the solution structure of <scene name='Journal:JBIC:14/Cv/3'>C-terminus-truncated SlyD</scene> from ''Helicobacter pylori'' (HpSlyDΔC). HpSlyDΔC folds into <scene name='Journal:JBIC:14/Cv/4'>two well-separated, orientation-independent domains:</scene> the <font color='cyan'><b>PPIase-active FKBP domain (in cyan)</b></font> and the <font color='red'><b>chaperone-active insert-in-flap (IF) domain (in red)</b></font>, <font color='darkmagenta'><b>linkers are in darkmagenta</b></font>. The FKBP domain consists of a four-stranded antiparallel β-sheet with an α-helix on one side, whereas the IF domain folds into a four-stranded antiparallel β-sheet accompanied by a short α-helix. Intact ''H. pylori'' SlyD binds both Ni²⁺ and Zn²⁺, with dissociation constants of 2.74 and 3.79 μM respectively. Intriguingly, binding of Ni²⁺ instead of Zn²⁺ induces protein conformational changes around the active sites of the FKBP domain, implicating a regulatory role of nickel. The twin-arginine translocation (Tat) signal peptide from the small subunit of [NiFe] hydrogenase (HydA) binds the protein at the IF domain. Nickel binding and the recognition of the Tat signal peptide by the protein suggest that SlyD participates in [NiFe] hydrogenase maturation processes.