Escherichia coli Requires the Protease Activity of FtsH for Growth

Jayasekera, Maithri M.K.; Foltin, Susan K.; Olson, Eric R.; Holler, Tod P.

doi:10.1006/abbi.2000.1903

Cited by 25 publications

(21 citation statements)

References 27 publications

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“…5 FtsH is the only essential ATP-dependent protease in E. coli. 6 It is a metalloprotease containing Zn 2+ at the active site of the proteolytic chamber. 7 The FtsH holoenzyme is a ring-shaped homohexamer forming a complex of up to 1 MDa together with the membrane proteins QmcA and HflKC.…”

Section: Introductionmentioning

confidence: 99%

Sequence and Length Recognition of the C-terminal Turnover Element of LpxC, a Soluble Substrate of the Membrane-bound FtsH Protease

Führer

Müller

Baumann

et al. 2007

Journal of Molecular Biology

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Section: Introductionmentioning

confidence: 99%

Sequence and Length Recognition of the C-terminal Turnover Element of LpxC, a Soluble Substrate of the Membrane-bound FtsH Protease

Führer

Müller

Baumann

et al. 2007

Journal of Molecular Biology

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“…FtsH (HflB) is an ATP-dependent, membrane-bound protease (17,18) which belongs to the AAA family (ATPases associated with diverse cellular activities) (2,26,31,36). FtsH degrades proteins tagged with the SsrA degradation peptide (12,13) as well as YccA, SecY, and the ATPase F 0 when they are not complexed (1,20).…”

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confidence: 99%

Dual Role of FtsH in Regulating Lipopolysaccharide Biosynthesis in Escherichia coli

Katz

Ron

2008

J Bacteriol

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In Escherichia coli, FtsH (HflB) is a membrane-bound, ATP-dependent metalloendoprotease belonging to the AAA family (ATPases associated with diverse cellular activities). FtsH has a limited spectrum of known substrates, including the transcriptional activator 32 . FtsH is the only known E. coli protease that is essential, as it regulates the concentration of LpxC, which carries out the first committed step in the synthesis of lipid A. Here we identify a new FtsH substrate-3-deoxy-D-manno-octulosonate (KDO) transferase-which carries out the attachment of two KDO residues to the lipid A precursor (lipid IV A ) to form the minimal essential structure of the lipopolysaccharide (LPS) (KDO 2 -lipid A). Thus, FtsH regulates the concentration of the lipid moiety of LPS (lipid A) as well as the sugar moiety (KDO-based core oligosaccharides), ensuring a balanced synthesis of LPS.FtsH (HflB) is an ATP-dependent, membrane-bound protease (17, 18) which belongs to the AAA family (ATPases associated with diverse cellular activities) (2,26,31,36). FtsH degrades proteins tagged with the SsrA degradation peptide (12, 13) as well as YccA, SecY, and the ATPase F 0 when they are not complexed (1,20). FtsH also has an important regulatory role in Escherichia coli, as it specifically degrades proteins such as the transcriptional activator 32 and the viral regulatory proteins CII, CIII, and Xis (5,14,15,21,35,37). However, although FtsH regulates the concentration of several key proteins, the spectrum of its specific substrates is quite limited.FtsH is the only known essential ATP-dependent protease in E. coli. The lack of viability of ⌬ftsH mutants is due to the accumulation of UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC), which catalyzes the second reaction and the first committed step in the biosynthesis of lipid A (9, 30). The accumulation of LpxC results in unbalanced ratio of lipid A (in the biosynthesis of lipopolysaccharides [LPS]) to phospholipids, as both pathways use the same precursor (-3-hydroxymyristoyl-acyl carrier protein), which is present in limited amounts (30).LPS is an essential component of the outer membrane of gram-negative bacteria and is present in high concentrations (about 10% of the total cell lipids). LPS is vital for bacterial pathogenesis, as virulence of mutants with altered LPS is substantially decreased or eliminated. Moreover, LPS-also referred to as endotoxin-is highly toxic and constitutes the major lethal factor in gram-negative bacterial sepsis (24,27,33,34).LPS is composed of lipid A and core oligosaccharides which start with 2 units of 3-deoxy-D-manno-octulosonate (KDO). The KDO residues are transferred in two sequential steps to lipid IV A , the lipid A precursor, by the bifunctional enzyme KDO transferase (KdtA) (4). KDO 2 -lipid A represents the minimal essential structure of the LPS and, therefore, KdtA is the only essential glycosyltransferase in the core oligosaccharide biosynthesis pathway. It should be noted that recent results indicate the abilities of several suppressor mutatio...

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“…6, which is published as supporting information on the PNAS web site). In bacteria, FtsH malfunction causes severe phenotypes like cell division defects and growth arrest (4,5) (reviewed in ref. 3).…”

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The molecular architecture of the metalloprotease FtsH

Bieniossek

Schalch

Bumann

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

152

136

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The ATP-dependent integral membrane protease FtsH is universally conserved in bacteria. Orthologs exist in chloroplasts and mitochondria, where in humans the loss of a close FtsH-homolog causes a form of spastic paraplegia. FtsH plays a crucial role in quality control by degrading unneeded or damaged membrane proteins, but it also targets soluble signaling factors like 32 and -CII. We report here the crystal structure of a soluble FtsH construct that is functional in caseinolytic and ATPase assays. The molecular architecture of this hexameric molecule consists of two rings where the protease domains possess an all-helical fold and form a flat hexagon that is covered by a toroid built by the AAA domains. The active site of the protease classifies FtsH as an Asp-zincin, contrary to a previous report. The different symmetries of protease and AAA rings suggest a possible translocation mechanism of the target polypeptide chain into the interior of the molecule where the proteolytic sites are located.AAA ͉ protease ͉ protein degradation ͉ x-ray A TP-dependent proteases play crucial roles in protein quality control and regulation (for reviews, see refs. 1 and 2). One of these is FtsH, initially described as a temperature-sensitive and cell-division-defective mutant, which is also called HflB, named after a high-frequency of lysogenization locus of bacteriophage . FtsH is an integral membrane protease found in bacteria, chloroplasts, and mitochondria (reviewed in ref.3) (Fig. 6, which is published as supporting information on the PNAS web site). In bacteria, FtsH malfunction causes severe phenotypes like cell division defects and growth arrest (4, 5) (reviewed in ref.3). Deletion of the human mitochondrial homolog paraplegin, which shares 40% sequence identity with FtsH from Escherichia coli, is responsible for an autosomal recessive form of hereditary spastic paraplegia (6). The N terminus of FtsH contains two transmembrane helices followed by an AAA module (ATPases associated with various cellular activities), including the SRH (second region of homology) (3). The C-terminal part of the polypeptide chain bears the HEXXH motif that is characteristic for Zn-dependent metalloproteases, where the two histidines coordinate to the zinc ion and the glutamate serves as a catalytic base. In bacteria, the AAA and protease domains are located on the cytosolic side of the membrane. Of the five ATP-dependent proteases in E. coli, HslVU, Lon, ClpXP, ClpAP, and FtsH, the last is the only one that is essential and universally conserved in bacteria. It degrades membrane proteins like the uncomplexed SecY subunit of translocase (7), the a-subunit of F o F 1 -ATPase (8), and the photosystem in chloroplasts (9), therefore playing an important role in the quality control of membrane proteins. Further targets comprise regulatory soluble proteins such as 32 (10, 11) or -CII transcriptional activator protein (12). All these substrates are degraded in an ATP-dependent manner where the energy is used for pulling the proteins out of the membran...

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Escherichia coli Requires the Protease Activity of FtsH for Growth

Cited by 25 publications

References 27 publications

Sequence and Length Recognition of the C-terminal Turnover Element of LpxC, a Soluble Substrate of the Membrane-bound FtsH Protease

Sequence and Length Recognition of the C-terminal Turnover Element of LpxC, a Soluble Substrate of the Membrane-bound FtsH Protease

Dual Role of FtsH in Regulating Lipopolysaccharide Biosynthesis in Escherichia coli

The molecular architecture of the metalloprotease FtsH

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