Activation of cell division protein FtsZ. Control of switch loop T3 conformation by the nucleotide gamma-phosphate.
The effect of bound nucleotide on the conformation of cell division protein FtsZ from Methanococcus jannaschii has been investigated using molecular dynamics and site-directed mutagenesis. The molecular dynamics indicate that the gamma-phosphate of GTP induces a conformational perturbation in loop T3 (Gly88-Gly99 segment), in a position structurally equivalent to switch II of Ha-ras-p21. In the simulated GTP-bound state, loop T3 is pulled by the gamma-phosphate into a more compact conformation than with GDP, related to that observed in the homologous proteins alpha- and beta-tubulin. The existence of a nucleotide-induced structural change in loop T3 has been confirmed by mutating Thr92 into Trp (T92W-W319Y FtsZ). This tryptophan (12 A away from gamma-phosphate) shows large differences in fluorescence emission, depending on which nucleotide is bound to FtsZ monomers. Loop T3 is located at a side of the contact interface between two FtsZ monomers in the current model of FtsZ filament. Such a structural change may bend the GDP filament upon hydrolysis by pushing against helix H8 of next monomer, thus, generating force on the membrane during cell division. A related curvature mechanism may operate in tubulin activation.
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Cientificas, C/Velázquez, 144, 28006 Madrid, Spain. fer@akilonia.cib.csic.es
J F
JF
Díaz
A
A
Kralicek
J
J
Mingorance
J M
JM
Palacios
M
M
Vicente
J M
JM
Andreu
D000595:Amino Acid Sequence; D019843:Archaeal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D002455:Cell Division; D005998:Glycine; D006153:Guanosine Diphosphate / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism*; D017017:Methanococcus / Q000166:cytology / Q000235:genetics / Q000502:physiology*; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism
D019843:Archaeal Proteins; C119586:FtsZ protein, Methanococcus jannaschii; D011994:Recombinant Proteins; D014404:Tubulin; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D005998:Glycine