Disease relevance of ECs1669

• The E. coli minicell locus (minB) was shown to code for three gene products (MinC, MinD, and MinE) whose coordinate action is required for proper placement of the division spetum [1].
• Polar localization of the MinD protein of Bacillus subtilis and its role in selection of the mid-cell division site [2].
• Conversely, overproduction of ZapA reversed the toxicity of excess levels of the division inhibitor MinD [3].
• In Escherichia coli, site selection is dependent on MinC, MinD and MINE: MinC acts, with MinD, to inhibit division at sites other than the midcell by directly interacting with FTSZ: Here we report the crystal structure to 2.2 A of MinC from Thermotoga maritima [4].
• MinD is involved in regulating the proper placement of the cytokinetic machinery in some bacteria, including Neisseria gonorrhoeae and Escherichia coli [5].

High impact information on ECs1669

• Topological regulation of cell division in E. coli. spatiotemporal oscillation of MinD requires stimulation of its ATPase by MinE and phospholipid [6].
• Alanine scanning mutational analyses of E.coli MinD were also performed in vivo [7].
• We show that the Min oscillations, including mutant phenotypes, can be accounted for by in vitro-observed interactions involving MinD and MinE, with a crucial role played by the rate of nucleotide exchange [8].
• Accurate positioning of the division septum at the equator of Escherichia coli cells requires a rapid oscillation of MinD ATPase between the polar halves of the cell membrane, together with the division inhibitor MinC, under MinE control [9].
• However, the mechanism by which MinD associates with the membrane has proved enigmatic; it seems to lack a transmembrane domain and the amino acid sequence is devoid of hydrophobic tracts that might predispose the protein to interaction with lipids [10].

Chemical compound and disease context of ECs1669

• To investigate whether E. coli MinD displays a preference for anionic phospholipids, we first examined the localization dynamics of a green fluorescent protein-tagged derivative of MinD expressed in a mutant of E. coli that lacks phosphatidylethanolamine [11].
• These include a mammalian tyrosine kinase substrate; the Escherichia coli cell cycle protein MinD; the human inositol polyphosphate-5-phosphatase (gene OCRL) involved in Lowe's syndrome, a developmental disorder; and helicases, for which the new yeast member defines a distinct DEAD/H-box subfamily [12].

Biological context of ECs1669

• In Escherichia coli precise Z-ring placement at midcell depends on controlled oscillatory behavior of MinD and MinE: In the presence of ATP MinD interacts with the FtsZ inhibitor MinC and migrates to the membrane where the MinD-MinC complex recruits MinE, followed by MinD-mediated ATP hydrolysis and membrane release [13].
• Oligomerization of MinD on the liposome surface also was detected by fluorescence resonance energy transfer between MinD molecules labeled with different fluorescent probes [11].
• We suggest a model in which the ATP-dependent dimerization of MinD affects the conformation of the C-terminal region, a potential amphipathic helix, triggering membrane binding [14].
• A conserved sequence at the C-terminus of MinD is required for binding to the membrane and targeting MinC to the septum [14].
• DNA sequence analysis found two open reading frames whose predicted products had significant identity to the E. coli MinC cell division inhibitor and the MinD ATPase activator of MinC, and disruption of minCD function generated a minicell phenotype in B. subtilis [15].

Anatomical context of ECs1669

• Emphasizing generic properties of the protein dynamics, two features are found to be sufficient for generating oscillations: first, a tendency of membrane bound MinD to cluster; and second, attachment to and detachment from the cell wall, which depends on the amount of molecules already attached [16].
• Targeting to the nuclear membrane was equally effective using the intrinsic MinD membrane-targeting domain or the completely unrelated membrane-targeting domain of cytochrome b(5) [17].

Associations of ECs1669 with chemical compounds

• Lysine 11 is required for interaction of MinD with the membrane, MinC, MinE, and itself [18].
• Each MinC mutant interacted with either MinC or MinD but not both, indicating the specificity of glycine residues for particular protein-protein interactions [19].
• CONCLUSIONS: Structure analysis shows that MinD is most similar to nitrogenase iron protein, which is a member of the P loop-containing nucleotide triphosphate hydrolase superfamily of proteins [20].

Analytical, diagnostic and therapeutic context of ECs1669

• When the putative ATP binding domain of MinD was altered by site-directed mutagenesis, the mutant protein was no longer able to activate the MinC-dependent division inhibition system [21].
• Immunoelectron microscopy showed that MinD was located in the inner membrane region of the cell envelope [21].
• Western blot analysis verified the absence of MinD from N. gonorrhoeae (MinD(Ng)) in this mutant [22].
• The MinD protein from the hyperthermophilic archaeon Pyrococcus horikoshii: crystallization and preliminary X-ray analysis [23].

References