Crystal structure of a PCP/Sfp complex reveals the structural basis for carrier protein posttranslational modification.
Phosphopantetheine transferases represent a class of enzymes found throughout all forms of life. From a structural point of view, they are subdivided into three groups, with transferases from group II being the most widespread. They are required for the posttranslational modification of carrier proteins involved in diverse metabolic pathways. We determined the crystal structure of the group II phosphopantetheine transferase Sfp from Bacillus in complex with a substrate carrier protein in the presence of coenzyme A and magnesium, and observed two protein-protein interaction sites. Mutational analysis showed that only the hydrophobic contacts between the carrier protein's second helix and the C-terminal domain of Sfp are essential for their productive interaction. Comparison with a similar structure of a complex of human proteins suggests that the mode of interaction is highly conserved in all domains of life.
Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University Frankfurt/Main, Max-von-Laue-Strasse 9, 60438 Frankfurt, Germany; Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt/Main, Max-von-Laue-Strasse 15, 60438 Frankfurt, Germany.
Peter
P
Tufar
Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt/Main, Max-von-Laue-Strasse 15, 60438 Frankfurt, Germany; Institute of Biochemistry II, Goethe University Medical School, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Simin
S
Rahighi
Department of Chemistry, Biochemistry, Philipps University Marburg, Hans-Meerwein-Strasse, 35032 Marburg, Germany.
Femke I
FI
Kraas
Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University Frankfurt/Main, Max-von-Laue-Strasse 9, 60438 Frankfurt, Germany.
Donata K
DK
Kirchner
Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University Frankfurt/Main, Max-von-Laue-Strasse 9, 60438 Frankfurt, Germany.
Frank
F
Löhr
Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University Frankfurt/Main, Max-von-Laue-Strasse 9, 60438 Frankfurt, Germany.
Erik
E
Henrich
Max Planck Institute of Biophysics, Department of Molecular Membrane Biology, Max-von-Laue-Strasse 3, 60438 Frankfurt, Germany.
Jürgen
J
Köpke
Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt/Main, Max-von-Laue-Strasse 15, 60438 Frankfurt, Germany; Institute of Biochemistry II, Goethe University Medical School, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Ivan
I
Dikic
Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University Frankfurt/Main, Max-von-Laue-Strasse 9, 60438 Frankfurt, Germany.
Peter
P
Güntert
Department of Chemistry, Biochemistry, Philipps University Marburg, Hans-Meerwein-Strasse, 35032 Marburg, Germany.
Mohamed A
MA
Marahiel
Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University Frankfurt/Main, Max-von-Laue-Strasse 9, 60438 Frankfurt, Germany; Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt/Main, Max-von-Laue-Strasse 15, 60438 Frankfurt, Germany. Electronic address: vdoetsch@em.uni-frankfurt.de.
Volker
V
Dötsch
D000213:Acyl Carrier Protein / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000201:enzymology; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D017855:Transferases (Other Substituted Phosphate Groups) / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D000213:Acyl Carrier Protein; D001426:Bacterial Proteins; D002352:Carrier Proteins; C082662:phosphopantetheinyl transferase; D017855:Transferases (Other Substituted Phosphate Groups)