Disease relevance of ECs4057

• Degradation of carboxy-terminal-tagged cytoplasmic proteins by the Escherichia coli protease HflB (FtsH) [1].
• Host regulation of lysogenic decision in bacteriophage lambda: transmembrane modulation of FtsH (HflB), the cII degrading protease, by HflKC (HflA) [2].
• The FtsH protease is involved in development, stress response and heat shock control in Caulobacter crescentus [3].
• Cloning and expression of the gene coding for FtsH protease from Mycobacterium tuberculosis H37Rv [4].
• SpoVM, a small protein essential to development in Bacillus subtilis, interacts with the ATP-dependent protease FtsH [5].

High impact information on ECs4057

• Lack of a robust unfoldase activity confers a unique level of substrate specificity to the universal AAA protease FtsH [6].
• Because FtsH lacks robust unfoldase activity, it is able to use the protein folding state of substrates as a criterion for degradation [6].
• We suggest that the cytoplasmic domain has intrinsic but weak self-interaction ability, which becomes effective with the aid of the leucine zipper or membrane tethering, and that membrane association is essential for FtsH to degrade integral membrane proteins [7].
• A protease complex in the Escherichia coli plasma membrane: HflKC (HflA) forms a complex with FtsH (HflB), regulating its proteolytic activity against SecY [8].
• Furthermore cross-linking, co-immunoprecipitation, histidine-tagging and gel filtration experiments all indicated that FtsH and HflKC form a complex in vivo and in vitro [8].

Chemical compound and disease context of ECs4057

• Like other AAA proteins, Escherichia coli FtsH, a membrane-bound AAA protease, contains highly conserved aromatic and glycine residues (Phe228 and Gly230) that are predicted to lie in the central pore region of the hexamer [9].
• Sequence alignment indicates that glutamic acid residues are conserved among the FtsH homologues at positions corresponding to Glu(479) and Glu(585) of E. coli FtsH [10].
• The ATPase domain of FtsH from Escherichia coli has been crystallized from ammonium sulfate solutions and crystals diffracting to 1.5 A resolution have been obtained [11].

Biological context of ECs4057

• FtsH has a zinc-binding motif similar to the active site of zinc-metalloproteases [12].
• We report here that FtsH is involved in degradation of the heat-shock transcription factor sigma 32, a key element in the regulation of the E. coli heat-shock response [12].
• The primary light-induced cleavage product of the D1 protein, a 23-kD fragment, was found to be degraded in isolated thylakoids in the dark during a process dependent on ATP hydrolysis and divalent metal ions, suggesting the involvement of FtsH [13].
• Suppressor mutations of ftsH1 temperature-sensitive lethality, located in the fur gene (coding for the ferric uptake regulator), did not restore FtsH/HflB activity with respect to lambda lysogenization [14].
• Yme1p is most similar to the Escherichia coli FtsH protein, an essential protein involved in septum formation during cell division [15].

Anatomical context of ECs4057

• The thylakoid FtsH protease plays a role in the light-induced turnover of the photosystem II D1 protein [13].
• Purified FtsH degraded the 23-kD D1 fragment present in isolated photosystem II core complexes, as well as that in thylakoid membranes depleted of endogenous FtsH [13].
• Unlike previously identified membrane-bound substrates for FtsH in bacteria and mitochondria, the 23-kD D1 fragment represents a novel class of FtsH substrate-functionally assembled proteins that have undergone irreversible photooxidative damage and cleavage [13].
• The FtsH action is processive and presumably involves dislocation of the substrate from the membrane to the cytosol [16].
• FtsH is an Escherichia coli protein with its amino-terminal region anchored to the cytoplasmic membrane and with its cytoplasmic domain significantly homologous to the members of an ATPase family found in eukaryotic cells [17].

Associations of ECs4057 with chemical compounds

• Protease activity of FtsH for histidine-tagged sigma 32 was stimulated by Zn2+ and strongly inhibited by the heavy metal chelating agent o-phenanthroline [12].
• In vitro casein degradation by membrane-integrated FtsH was stimulated by succinate, a respiratory substrate; this stimulation was counteracted by cyanide-3-chlorophenylhydrazone [18].
• In this study, we show that FtsH-dependent degradation of both membrane-bound and soluble proteins is retarded when cells are treated with carbonyl cyanide-3-chlorophenylhydrazone or 2,4-dinitrophenol uncouplers, which dissipate the proton-motive force [18].
• We purified wild-type and mutant FtsH proteins by making use of a polyhistidine tag attached to their carboxyl termini [19].
• Moreover, treatment of membranes or their detergent extracts with a cross-linker, dithiobis(succinimidyl propionate), yielded cross-linked products of FtsH [20].

Analytical, diagnostic and therapeutic context of ECs4057

• Co-immunoprecipitation experiments confirmed the interaction between the FtsH molecules [20].
• Identification, characterization, and molecular cloning of a homologue of the bacterial FtsH protease in chloroplasts of higher plants [21].
• Dissecting the role of a conserved motif (the second region of homology) in the AAA family of ATPases. Site-directed mutagenesis of the ATP-dependent protease FtsH [22].
• Electron microscopy revealed that purified FtsH forms ring-shaped structures with a diameter of 6-7 nm [23].
• The presence of the coiled-coil motif in the Escherichia coli FtsH (HflB) was demonstrated by circular dichroism and cross-linking experiments [24].

References