The stathmin-derived I19L peptide interacts with FtsZ and alters its bundling.
FtsZ is a prokaryotic tubulin-like protein. Despite a low degree of sequence identity with tubulin, it presents the same folding pattern and some similar functions, notably in cell division. Indeed, FtsZ and tubulin polymerize to form bundles and microtubules, respectively, which are essential for cell cytokinesis. We previously demonstrated that peptides derived from the N-terminal stathmin domain interact with tubulin and impede microtubule formation. We demonstrated here that I19L, the most efficient of these peptides, also alters FtsZ bundling assembly in vitro. STD-NMR and TRNOESY experiments revealed that I19L interacts with FtsZ and folds upon its binding but in a way different from what we observed with tubulin. These NMR data were used in molecular modeling calculations to propose models of the I19L-FtsZ complex. Interestingly, two models, consistent with NMR data, show an interaction of I19L near the T7 loop or near the GTP binding site of FtsZ, explaining the modifications of the bundling assembly observed with this peptide. The fine analysis of the structural differences of the complexes of I19L with FtsZ and tubulin should help for the rational development of new specific antibiotic agents.
Clément
Marie-Jeanne
MJ
Laboratoire Structure-Activité des Biomolécules Normales et Pathologiques, INSERM/UEVE U829, Evry, 91025 France.
Kuoch
Boï-trinh
BT
Ha-Duong
Tap
T
Joshi
Vandana
V
Hamon
Loïc
L
Toma
Flavio
F
Curmi
Patrick A
PA
Savarin
Philippe
P
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D002455:Cell Division; D003598:Cytoskeletal Proteins / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D018625:Microscopy, Atomic Force / Q000379:methods; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification; D011487:Protein Conformation; D017510:Protein Folding; D050777:Stathmin / Q000737:chemistry*; D013816:Thermodynamics; D014404:Tubulin / Q000737:chemistry
D001426:Bacterial Proteins; D003598:Cytoskeletal Proteins; C071525:FtsZ protein, Bacteria; D010446:Peptide Fragments; D050777:Stathmin; D014404:Tubulin