FtsH – a single-chain charonin?

Abstract

The ftsH gene encodes an ATP- and Zn(2+)-dependent metalloprotease with a molecular mass of about 70 kDa. It was first identified in Escherichia coli where it is also designated hflB, tolZ or mrsC, and seems to be present in most if not all bacteria. The FtsH protein is anchored to the cytoplasmic membrane via two transmembrane regions in such a way that the very short amino- and the long carboxy-termini are exposed into the cytoplasm. FtsH is member of the AAA family (ATPases associated with a variety of cellular activities) which are characterized by a module of about 200 amino acid residues in length containing an ATP-binding site. In Escherichia coli, FtsH forms a complex with a pair of periplasmically exposed membrane proteins, HflK and HflC. The E. coli enzyme is required for proteolytic degradation of some unstable proteins that include both soluble regulatory proteins such as sigma 32 (heat-shock sigma factor) and phage lambda CII (transcriptional activator), and membrane proteins including uncomplexed forms of SecY (forms the translocon together with SecE and SecG) and the a subunit of the F0 complex of the H(+)-ATPase. Its activity can be modulated by the HflKC proteins, by another membrane protein designated YccA which can transiently associate with both the FtsH and the HflKC proteins, or by small peptides such as CIII encoded by phage lambda (involved in lysogenization) or SpoVM (needed for sporulation) encoded by Bacillus subtilis. Besides being a protease, there is circumstantial evidence that FtsH also acts as a molecular chaperone. It influences protein assembly in and through the cytoplasmic membrane and associates with denatured alkaline phosphatase without degrading it. Therefore, FtsH may serve to maintain quality control of some cytoplasmic and membrane proteins. Such ATP-dependent proteases with intrinsic chaperone activity have been designated charonins.

Interplay Between N-Terminal Methionine Excision and FtsH Protease Is Essential for Normal Chloroplast Development and Function in Arabidopsis

“…We propose two nonexclusive hypotheses: i) the absence of FtsH2, which leads to lower levels of the FtsH complex, increases the proteolytic activity of other chloroplastic proteases; and ii) the FtsH complex is a chaperone for newly synthesized proteins. This second hypothesis is further supported by the chaperone activity demonstrated for the bacterial and mitochondrial FtsH homologs (Shirai et al, 1996;Suzuki et al, 1997;Schumann, 1999;Sakamoto, 2006). We provide experimental evidence that correctly NMEprocessed N termini of D1 and D2 are indispensable for both FtsH-mediated quality control of the proteins and repair-related degradation of D1 and D2.…”

Role of the hprT–ftsH locus in Staphylococcus aureus

“…The hprTftsH gene arrangement (Fig. 1) is similar in S. aureus, B. subtilis and Listeria monocytogenes, but not in all bacteria (Schumann, 1999). Considering the multiple functions and essentiality of ftsH in many bacteria, it was of interest to determine the role of this gene in S. aureus.…”

α-Crystallin-Type Heat Shock Proteins: Socializing Minichaperones in the Context of a Multichaperone Network

“…Most intriguingly, the proteases involved in protein quality control have intrinsic chaperone activity, either within the same polypeptide (Lon, FtsH, and DegP) or located in associated components of a protease complex (ClpAP and ClpXP, where the ATP-dependent chaperone is underlined). The term "charonin" was invented for this type of multifunctional proteins or protein complexes (97,272,338). The tight FIG.…”