Escherichia coli FtsH is a membrane-bound, ATP-dependent protease which degrades the heat-shock transcription factor sigma 32.

Abstract

Escherichia coli FtsH is an essential integral membrane protein that has an AAA-type ATPase domain at its C-terminal cytoplasmic part, which is homologous to at least three ATPase subunits of the eukaryotic 26S proteasome. We report here that FtsH is involved in degradation of the heat-shock transcription factor a32, a key element in the regulation of the E.coli heat-shock response. In the temperature-sensitive ftsHJ mutant, the amount of aY32 at a non-permissive temperature was higher than in the wild-type under certain conditions due to a reduced rate of degradation. In an in vitro system with purified components, FtsH catalyzed ATPdependent degradation of biologically active histidinetagged &32. FtsH has a zinc-binding motif similar to the active site of zinc-metalloproteases. Protease activity of FtsH for histidine-tagged a32 was stimulated by Zn2+ and strongly inhibited by the heavy metal chelating agent o-phenanthroline. We conclude that FtsH is a novel membrane-bound, ATP-dependent metalloprotease with activity for a32. These findings indicate a new mechanism of gene regulation in E.coli.

The Evolution of the Conserved ATPase Domain (CAD): Reconstructing the History of an Ancient Protein Module

“…Nearly all eubacterial CADs belong to a monophyletic protein group that encodes membrane-bound metalloproteases, as exemplified by the Escherichia coli ftsH protein (Tomoyasu et al 1995). This metalloprotease group is strongly supported as a clade in our analysis, with a bootstrap level of 100% (Fig.…”

“…Both the ATPase activity and Zn-binding activity are required for the correct functioning of these proteins (Weber et al 1996). Members of this protein group have been shown to degrade transcription factors such as 32 (Tomoyasu et al 1995;Herman et al 1995) and phage cII (Arlt et al 1996) protein and probably participate in a number of other cellular functions as well. The E. coli ftsH protein, for example, is also involved in bacterial septum formation (Santoss and De Almeida et al 1975), probably via secretory processes (Kihara et al 1995; Akiyama et al 1996).…”

“…Although the domain contains a Walker Type I ATPase motif that is essential for protein function, the CAD is clearly different from other ATPase protein families such as DEAD-box helicases (Hodgman 1992), ion pumps, and ABC transporters (Fath and Kolter 1993). Members of the CADcontaining AAA family have been shown to participate in vesicle fusion (Sollner et al 1993), peroxisomal protein import (Heyman et al 1994), mitochondrial membrane-bound proteolysis (Guelin et al 1994;Tomoyasu et al 1995), cell cycle control (Frohlich et al 1991), proteasomal regulation Dubiel et al 1995), mitotic spindle formation (Clark-Maquire and Mains 1994), signal transduction (Schulte et al 1994), protein complex formation (Nobrega et al 1992; Paul and Tzagoloff 1995) and possibly transcription (Swaffield et al 1995;Lee et al 1995;Xu et al 1995). Considering different facets of each known biological activity attributed to AAA proteins, Confalonieri and Duguet (1995) have proposed two unifying functions for CADs: (1) an ATP-dependent proteasomal or chaperone function and (2) an ability to act as an ATP-depending anchorage, or ''protein clamp.…”

Identification of Salt-Tolerant Sinorhizobium sp. Strain BL3 Membrane Proteins Based on Proteomics

“…Among these groups of protein, a group of membrane protease proteins (SMc01135, SMc01440, SMc01441, and SMc04459) were identified. Proteases are important components of complex regulatory networks to cope with environmental stress in many organisms (39,42). SMc04459 (FtsH) has previously been identified in nodule bacteria (9).…”

The role of protein degradation in mitochondrial function and biogenesis

“…The homologue of these proteins in E. coli, FtsH, governs the degradation of the soluble proteins λ-cII (Herman et al 1993), λ-cIII and σ 32 (Herman et al 1995;Tomoyasu et al 1995) in addition to being involved in degrading the integral membrane protein SecY (Kihara et al 1995). Significantly, in vitro degradation of σ 32 by purified FtsH is the first direct proof of ATP-and divalent metal-dependent protease activity of a member of the FtsH-subfamily (Tomoyasu et al 1995). …”