Structural reorganization of the bacterial cell-division protein FtsZ fromStaphylococcus aureus

Abstract

FtsZ is a key molecule in bacterial cell division. In the presence of GTP, it polymerizes into tubulin-like protofilaments by head-to-tail association. Protofilaments of FtsZ seem to adopt a straight or a curved conformation in relation to the bound nucleotide. However, although several bacterial and archaeal FtsZ structures have been determined, all of the structures reported previously are considered to have a curved conformation. In this study, structures of FtsZ from Staphylococcus aureus (SaFtsZ) were determined in apo, GDP-bound and inhibitor-complex forms and it was found that SaFtsZ undergoes marked conformational changes. The accumulated evidence suggests that the GDP-bound structure has the features of the straight form. The structural change between the curved and straight forms shows intriguing similarity to the eukaryotic cytoskeletal protein tubulin. Furthermore, the structure of the apo form showed an unexpectedly large conformational change in the core region. FtsZ has also been recognized as a novel target for antibacterial drugs. The structure of the complex with the inhibitor PC190723, which has potent and selective antistaphylococcal activity, indicated that the inhibitor binds at the cleft between the two subdomains.

FtsZ filament capping by MciZ, a developmental regulator of bacterial division

“…Thus, the Asp280-Arg20 salt bridge is critical for complex stability. (10) showed that the presence of MciZ would completely prevent the association of FtsZ monomers (Fig. 1D).…”

“…FtsZ and tubulin share several essential properties: their assembly is cooperative, stimulated by GTP, and leads to GTP hydrolysis; they form dynamic polymers whose turnover is dependent on nucleotide hydrolysis (8); they use essentially the same bond for polymer formation (9); and recent evidence indicates that they undergo similar allosteric transitions upon polymerization (10,11). Not surprisingly, however, the functional specialization of these proteins led to some significant differences between them, the most prominent being that FtsZ exists as single protofilaments, whereas tubulin always adopts a multifilament tubular structure.…”

The Chloroplast Tubulin Homologs FtsZA and FtsZB from the Red Alga Galdieria sulphuraria Co-assemble into Dynamic Filaments

“…Huecas and Andreu (30) studied the effect of nucleotide in Methanococcus janaschii FtsZ and found that apo FtsZ assembled approximately the same as the GTP-bound and that addition of GDP caused rapid disassembly. Staphylococcus aureus FtsZ typically crystallizes in the form of assembled pfs (31,32), with GDP in the nucleotide pocket. The protein was purified without any nucleotide, so this implies that the GDP remained tightly bound during purification and crystallization.…”

Structural Change in FtsZ Induced by Intermolecular Interactions between Bound GTP and the T7 Loop

“…All of these structures were very similar, irrespective of the bound nucleotide, and the slight differences observed seemed to be related to interspecies differences (22). Recently, however, Staphylococcus aureus FtsZ (SaFtsZ) 3 has been shown to have a markedly different structure by sliding/rotation between two subdomains with concomitant conformational change of the T7 loop (23). This structure seemed to be related to the polymerization state; the T7 loop of the "upper" subunit in SaFtsZ was inserted more deeply into the nucleotide-binding pocket of the "lower" subunit than any other structure determined to date.…”

“…This structure seemed to be related to the polymerization state; the T7 loop of the "upper" subunit in SaFtsZ was inserted more deeply into the nucleotide-binding pocket of the "lower" subunit than any other structure determined to date. Therefore, the SaFtsZ structure has been interpreted as representing a straight protofilament conformation, whereas other structures are curved (and relaxed) conformations (23). This view is reinforced by the observation that SaFtsZ bound with PC190723, which inhibits GTPase activity by stabilizing the polymer formation (24), has the same conformation (23,25,26).…”