Theprokaryotic cytoskeleton is the collective name for all structuralprotein filaments inprokaryotes.[2] Some of these proteins areanalogues of those ineukaryotes, while others are unique to prokaryotes.[3][4][5][6] Cytoskeletal elements play essential roles incell division, protection, shape determination, and polarity determination in various prokaryotes.[7][8]
FtsZ, the first identified prokaryotic cytoskeletal element, forms a filamentous ring structure located in the middle of the cell called the Z-ring that constricts duringcell division, similar to theactin-myosin contractile ring in eukaryotes.[2] The Z-ring is a highly dynamic structure that consists of numerous bundles of protofilaments that extend and shrink, although the mechanism behind Z-ring contraction and the number of protofilaments involved are unclear.[1] FtsZ acts as an organizer protein and is required for cell division. It is the first component of theseptum duringcytokinesis, and it recruits all other known cell division proteins to the division site.[9]
Despite this functional similarity toactin, FtsZ is homologous to eukaryaltubulin. Although comparison of theprimary structures of FtsZ and tubulin reveal a weak relationship, their 3-dimensional structures are remarkably similar. Furthermore, like tubulin,monomeric FtsZ is bound toGTP and polymerizes with other FtsZ monomers with the hydrolysis of GTP in a mechanism similar to tubulin dimerization.[10] Since FtsZ is essential for cell division in bacteria, this protein is a target for the design of newantibiotics.[11]There currently exist several models and mechanisms that regulate Z-ring formation, but these mechanisms depend on the species. Several rod shaped species, includingEscherichia coli andCaulobacter crescentus, use one or more inhibitors of FtsZ assembly that form a bipolar gradient in the cell, enhancing polymerization of FtsZ at the cell center.[12] One of these gradient-forming systems consists of MinCDE proteins (see below).
MreB is a bacterial protein believed to be homologous to eukaryalactin. MreB and actin have a weakprimary structure match, but are very similar in terms of 3-D structure and filament polymerization.
Almost all non-spherical bacteria rely on MreB to determine their shape. MreB assembles into a helical network of filamentous structures just under thecytoplasmic membrane, covering the whole length of the cell.[13] MreB determines cell shape by mediating the position and activity of enzymes that synthesizepeptidoglycan and by acting as a rigid filament under the cell membrane that exerts outward pressure to sculpt and bolster the cell.[1] MreB condenses from its normal helical network and forms a tight ring at theseptum inCaulobacter crescentus right before cell division, a mechanism that is believed to help locate its off-center septum.[14] MreB is also important for polarity determination in polar bacteria, as it is responsible for the correct positioning of at least four different polar proteins inC. crescentus.[14]
ParM is a cytoskeletal element that possesses a similar structure toactin, although it behaves functionally liketubulin. Further, it polymerizes bidirectionally and it exhibitsdynamic instability, which are both behaviors characteristic of tubulin polymerization.[4][15] It forms a system with ParR andparC that is responsible forR1 plasmid separation. ParM affixes to ParR, aDNA-binding protein that specifically binds to 10 direct repeats in theparC region on the R1 plasmid. This binding occurs on both ends of the ParM filament. This filament is then extended, separating the plasmids.[16] The system is analogous to eukaryotic chromosome segregation as ParM acts like eukaryotictubulin in themitotic spindle, ParR acts like thekinetochore complex, andparC acts like thecentromere of thechromosome.[17]
F plasmid segregation occurs in a similar system where SopA acts as the cytoskeletal filament and SopB binds to thesopC sequence in the F plasmid, like thekinetochore andcentromere respectively.[17] Lately an actin-like ParM homolog has been found in agram-positive bacteriumBacillus thuringiensis, which assembles into a microtubule-like structure and is involved inplasmid segregation.[18]
Crenactin is an actin homologue unique to thearchaealphylumThermoproteota (formerly "Crenarchaeota") that has been found in the orderThermoproteales and genus "Candidatus Korarchaeum."[19] At the time of its discovery in 2009, it has the highest sequence similarity to eukaryotic actins of any known actin homologue.[20] Crenactin has been well characterized inPyryobaculum calidifontis (A3MWN5) and shown to have high specificity for ATP and GTP.[19] Species containing crenactin are all rod or needle shaped. InP. calidifontis, crenactin has been shown to form helical structures that span the length of the cell, suggesting a role for crenactin in shape determination similar to that of MreB in other prokaryotes.[19][21]
Even closer to the eukaryotic actin system is found in the archaealkingdomPromethearchaeati. They use primitive versions ofprofilin,gelsolin, andcofilin to regulate thecytoskeleton.[22]
Crescentin (encoded bycreS gene) is an analogue of eukaryoticintermediate filaments (IFs). Unlike the other analogous relationships discussed here, crescentin has a rather large primary homology with IF proteins in addition to three-dimensional similarity - the sequence ofcreS has a 25% identity match and 40% similarity tocytokeratin 19 and a 24% identity match and 40% similarity tonuclear lamin A. Furthermore, crescentin filaments are roughly 10 nm in diameter and thus fall within diameter range for eukaryal IFs (8-15 nm).[23] Crescentin forms a continuous filament from pole to pole alongside the inner, concave side of the crescent-shaped bacteriumCaulobacter crescentus. Both MreB and crescentin are necessary forC. crescentus to exist in its characteristic shape; it is believed that MreB molds the cell into a rod shape and crescentin bends this shape into a crescent.[1]
The MinCDE system is a filament system that properly positions theseptum in the middle of the cell inEscherichia coli. According to Shih et al., MinC inhibits the formation of the septum by prohibiting the polymerization of the Z-ring. MinC, MinD, and MinE form a helix structure that winds around the cell and is bound to the membrane by MinD. The MinCDE helix occupies a pole and terminates in a filamentous structure called the E-ring made of MinE at the middle-most edge of the polar zone. From this configuration, the E-ring will contract and move toward that pole, disassembling the MinCDE helix as it moves along. Concomitantly, the disassembled fragments will reassemble at the opposite polar end, reforming the MinCDE coil on the opposite pole while the current MinCDE helix is broken down. This process then repeats, with the MinCDE helix oscillating from pole to pole. This oscillation occurs repeatedly during the cell cycle, thereby keeping MinC (and its septum inhibiting effect) at a lower time-averaged concentration at the middle of the cell than at the ends of the cell.[24]
The dynamic behavior of the Min proteins has been reconstituted in vitro using an artificial lipid bilayer as mimic for the cell membrane. MinE and MinD self-organized into parallel and spiral protein waves by a reaction-diffusion like mechanism.[25]
Bactofilin (InterPro: IPR007607) is a β-helical cytoskeletal element that forms filaments throughout the cells of therod-shaped proteobacteriumMyxococcus xanthus.[26] The bactofilin protein, BacM, is required for proper cell shape maintenance and cell wall integrity.M. xanthus cells lacking BacM have a deformed morphology characterized by a bent cell body, andbacM mutants have decreased resistance to antibiotics targeting the bacterial cell wall.M. xanthus BacM protein is cleaved from its full-length form to allow polymerization. Bactofilins have been implicated in cell shape regulation in other bacteria, including curvature ofProteus mirabilis cells,[27] stalk formation byCaulobacter crescentus,[28] and helical shape ofHelicobacter pylori.[29]
