NMR solution structure and dynamics of the peptidyl-prolyl cis-trans isomerase domain of the trigger factor from Mycoplasma genitalium compared to FK506-binding protein.
We have solved the solution structure of the peptidyl-prolyl cis-trans isomerase (PPIase) domain of the trigger factor from Mycoplasma genitalium by homo- and heteronuclear NMR spectroscopy. Our results lead to a well-defined structure with a backbone rmsd of 0.23 A. As predicted, the PPIase domain of the trigger factor adopts the FK506 binding protein (FKBP) fold. Furthermore, our NMR relaxation data indicate that the dynamic behavior of the trigger factor PPIase domain and of FKBP are similar. Structural variations when compared to FKBP exist in the flap region and within the bulges of strand 5 of the beta sheet. Although the active-site crevice is similar to that of FKBP, subtle steric variations in this region can explain why FK506 does not bind to the trigger factor. Sequence variability (27% identity) between trigger factor and FKBP results in significant differences in surface charge distribution and the absence of the first strand of the central beta sheet. Our data indicate, however, that this strand may be partially structured as "nascent" beta strand. This makes the trigger factor PPIase domain the most minimal representative of the FKBP like protein family of PPIases.
Vogtherr
Martin
M
Institut für Organische Chemie der Universität Frankfurt, Marie-Curie-Str. 11, 60439 Frankfurt, Germany.
Jacobs
Doris M
DM
Parac
Tatjana N
TN
Maurer
Marcus
M
Pahl
Andreas
A
Saxena
Krishna
K
Rüterjans
Heinz
H
Griesinger
Christian
C
Fiebig
Klaus M
KM
D000595:Amino Acid Sequence; D001665:Binding Sites; D020134:Catalytic Domain; D017931:DNA Primers / Q000737:chemistry; D004926:Escherichia coli / Q000201:enzymology; D006639:Histidine / Q000737:chemistry; D006860:Hydrogen Bonding; D007536:Isomerism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009174:Mycoplasma / Q000201:enzymology* / Q000235:genetics; D019906:Nuclear Magnetic Resonance, Biomolecular; D019696:Peptidylprolyl Isomerase / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D022021:Tacrolimus Binding Proteins / Q000737:chemistry* / Q000378:metabolism
D017931:DNA Primers; D011993:Recombinant Fusion Proteins; D006639:Histidine; D022021:Tacrolimus Binding Proteins; D019696:Peptidylprolyl Isomerase