Structural and Functional Characterization of a Novel Family of Cyclophilins, the AquaCyps.
Cyclophilins are ubiquitous cis-trans-prolyl isomerases (PPIases) found in all kingdoms of life. Here, we identify a novel family of cyclophilins, termed AquaCyps, which specifically occurs in marine Alphaproteobacteria, but not in related terrestric species. In addition to a canonical PPIase domain, AquaCyps contain large extensions and insertions. The crystal structures of two representatives from Hirschia baltica, AquaCyp293 and AquaCyp300, reveal the formation of a compact domain, the NIC domain, by the N- and C-terminal extensions together with a central insertion. The NIC domain adopts a novel mixed alpha-helical, beta-sheet fold that is linked to the cyclophilin domain via a conserved disulfide bond. In its overall fold, AquaCyp293 resembles AquaCyp300, but the two proteins utilize distinct sets of active site residues, consistent with differences in their PPIase catalytic properties. While AquaCyp293 is a highly active general PPIase, AquaCyp300 is specific for hydrophobic substrate peptides and exhibits lower overall activity.
Departement Biozentrum, University of Basel, 4056, Basel, Switzerland.
Roman P
RP
Jakob
Laboratorium für Biochemie und Bayreuther Zentrum für Molekulare Biowissenschaften, Universität Bayreuth, D-95440, Bayreuth, Germany.
Philipp A M
PA
Schmidpeter
Laboratorium für Biochemie und Bayreuther Zentrum für Molekulare Biowissenschaften, Universität Bayreuth, D-95440, Bayreuth, Germany.
Johanna R
JR
Koch
Laboratorium für Biochemie und Bayreuther Zentrum für Molekulare Biowissenschaften, Universität Bayreuth, D-95440, Bayreuth, Germany.
Franz X
FX
Schmid
Departement Biozentrum, University of Basel, 4056, Basel, Switzerland.
Timm
T
Maier
D020561:Alphaproteobacteria / Q000201:enzymology*; D001426:Bacterial Proteins / Q000737:chemistry*; D002384:Catalysis; D018360:Crystallography, X-Ray; D021983:Cyclophilins / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D000072417:Protein Domains; D017433:Protein Structure, Secondary
D001426:Bacterial Proteins; D021983:Cyclophilins