Trends in Microbiology
ReviewThe ParA/MinD family puts things in their place
Section snippets
Positioning cellular components
Early microscopic observation of bacteria revealed the spatiotemporal regulation that must be operating within. Visible clues included a readily observable septum and, in some bacteria, the presence of a unipolar flagellum or polar type IV pili. Immunoelectron microscopy revealed the Z ring underlying the septum [1], and the advent of fluorescent technologies including GFP fusions revealed more clues, chromosomal origins, and plasmids duplicating and segregating to discrete cellular locations 2
The MinD/ParA family
ParA and MinD are ATPases but members of the large P loop GTPase superfamily [6]. This superfamily has two classes, TRAFAC and SIMIBI, and MinD/ParA are members of the latter class along with other related ATPases. Sequence and structure analysis allowed Liepe et al. [6] to identify eight subfamilies (Figure 1, black). Two of these, MinD and ParA, have been studied for some time and are fairly widely disseminated among bacteria, whereas most of the other related ATPases display a more limited
MinD/ParA are regulated by a nucleotide-dependent switch
The ATP form of MinD/ParA proteins is a dimer that usually binds to a surface that allows it to take up residency in the cell 18, 21, 22. MinD binds to the membrane using a C-terminal amphipathic helix, and ParA binds nonspecifically to DNA through positive charges located on one face of the protein 23, 24, 25, 26 (Figure 2b). Even though these proteins bind chemically different surfaces, the same face of the protein is used resulting in the same orientation on the surface. Dimerization brings
Oscillation (self-organizing) versus landmark (molecular beacon)
Proteins in bacteria localize by diffusion and capture [34], and ParA/MinD family members use two variations on this theme. One is an oscillatory mechanism observed with the Min and the plasmid ParA systems in E. coli 9, 35, 36. This mechanism is also likely to be used by some bacteria to position large protein structures (carboxysomes and large cytoplasmic chemotaxis clusters) [10]. The other is a landmark mechanism observed with the Min system in B. subtilis and with a chemotaxis system in
Min system: oscillation versus landmark
The Min system contributes to the spatial regulation of the Z ring in many bacteria by preventing its assembly away from midcell, especially near the poles [37]. The antagonist of FtsZ assembly, MinC, is activated and positioned in the cell through its interaction with MinD. The E. coli Min system is a pure oscillatory system, getting its spatial cues directly from the shape of the cell. The system is very responsive to the cell's shape and the pole-to-pole oscillation observed in wild-type
Segregating plasmids and protein clusters: an oscillatory mechanism
Three systems for segregating low copy plasmids have been classified based upon the nucleotide hydrolyzing enzyme that powers segregation [55]. For type I the ATPase is a ParA type, whereas for type II the ATPase (ParM) is related to actin. The third type employs a GTPase (TubZ) that it related to the FtsZ/tubulin family. Although the latter two employ dynamic filaments that push the plasmids apart, the ability to form cytoplasmic filaments is more controversial for the type I ParAs. Several of
Segregation of chromosomal origins: oscillation with cues and aids
ParAs are also involved in chromosome segregation, at least in bacteria that do not undergo multifork replication. In comparison to plasmid segregation, however, several extrinsic proteins are required to ensure the unidirectional movement of the chromosomal origin (Figure 4b). The process appears similar among the two organisms studied, V. cholerae [58] and Caulobacter crescentus 32, 59, 60, although more details are known about the latter. The cell cycle starts with the origin sequestered at
Two proteins, two gradients, one regulator
In C. crescentus, a distinct MinD/ParA member, MipZ, forms a bipolar gradient on the nucleoid to spatially regulate Z ring formation [14]. Like the ParA pattern in this organism, the bipolar MipZ gradient is dependent upon ParB and nonspecific DNA binding; however, its distribution on the nucleoid is temporally distinct from ParA (compare Figure 4, panels b and c). How can ParB cause two similar proteins to produce different patterns? The answer lies in the way ParB regulates the ATPase
A landmark mechanism for chemotaxis and type IV pili
As mentioned above, some orphan ParAs are involved in the distribution of chemotaxis protein clusters by using an oscillating mechanism that mimics plasmid partitioning. However, other ParAs (designated ParCs) position chemotaxis proteins using a landmark mechanism [9]. A newborn V. cholerae cell contains a ParC focus at the old pole, and as the cell cycle proceeds a new ParC focus develops at the new pole, so that following division each progeny cell inherits a cluster (Figure 5a). At no time
Variations and questions
Investigation into the Min systems of E. coli and B. subtilis has already revealed that MinD can use either an oscillatory or landmark mechanism depending upon its protein partners. Also, one clade of orphan ParAs (ParC) does not bind DNA and uses a landmark mechanism to localize chemotaxis proteins, whereas other orphan ParAs are closer to plasmid ParAs and use an oscillatory mechanism to segregate non-DNA cargo, such as cytoplasmic chemotaxis clusters. Although there have been extensive
Concluding remarks
The MinD/ParA family of proteins has evolved as a nucleotide-dependent switch that regulates its affinity for a surface and other proteins. In the best studied examples, the protein binds to a surface and the switch is activated by a partner that is spatially restricted leading to an oscillatory pattern. Patterns have been observed on membranes that regulate the positioning of the Z ring and on the nucleoid leading to segregation of plasmids, oriC regions, protein clusters, and positioning of
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