Conformational transition of the lid helix covering the protease active site is essential for the ATP‐dependent protease activity of FtsH

Abstract

FtsH and FtsH bind by molecular sieving (View Interaction)

Early emergence of the FtsH proteases involved in photosystem II repair

“…Sites 2 and 3, at positions 400-408 and 445-447, respectively, are close to the flexible glycine [G399 in T. thermophilus (Suno et al 2006, Vostrukhina et al 2015 and G404 in T. maritima (Bieniossek et al 2009)] and lid helix (Bieniossek et al 2009, Suno et al 2012 regions R443-E455 in T. thermophilus (Suno et al 2006, Vostrukhina et al 2015 (Fig. 5C), whose structural flexibility is considered crucial for the intradomain movements needed for full functionality of the complex (Bieniossek et al 2009, Suno et al 2012, Vostrukhina et al 2015.…”

“…5C), whose structural flexibility is considered crucial for the intradomain movements needed for full functionality of the complex (Bieniossek et al 2009, Suno et al 2012, Vostrukhina et al 2015. Mutations in the lid helix lead to a decrease of not only the protease activity but also the ATPase activity (Suno et al 2012), strongly indicating the lid helix and flexible glycine interact with each other. CyanoFtsH4 possesses a conserved leucine at position 400 and 447, in contrast to the highly flexible proline and glycine found in cyanoFtsH3 at these respective positions.…”

The structure of Aquifex aeolicus FtsH in the ADP-bound state reveals a C 2-symmetric hexamer

“…For FtsH, the most complete currently available crystal structures comprise the whole cytosolic regions of the enzymes from Thermotoga maritima (Á-TmFtsH) at 2.44 Å resolution (Bieniossek et al, 2006) and from Thermus thermophilus (Á-TtFtsH) at 3.9 Å resolution (Suno et al, 2006(Suno et al, , 2012. Both show a homohexameric architecture built by two separate rings that are formed by the AAA and protease domains, respectively.…”

Large conformational changes in FtsH create an opening for substrate entry

“…Structural studies have used truncated FtsH forms with only the soluble C-terminal (cytosolic) part (Bieniossek et al, 2009; Bieniossek et al, 2006; Kim et al, 2008; Niwa et al, 2002; Suno et al, 2006; Suno et al, 2012; Vostrukhina et al, 2015) or with only the periplasmic domain (Scharfenberg et al, 2015). The single full-length structure concerns m -AAA, the yeast mitochondrial ortholog of bacterial FtsH, which has been resolved at 12 Å resolution by cryo-electron microscopy (Lee et al, 2011).…”

“…These different conformations suggest that the ATPase domain could move polypeptides in steps as long as 45 Å into the central cavity during ATP hydrolysis cycles (Bieniossek et al, 2009). In contrast, the C-terminal protease domain always shows a six-fold symmetry for all crystal structures, i.e., the cytosolic domain of Thermus thermophiles FtsH (Suno et al, 2012), of Thermotoga maritima FtsH (Bieniossek et al, 2009; Bieniossek et al, 2006) and of Aquifex aeolicus FtsH (Suno et al, 2006; Vostrukhina et al, 2015). The proposed mechanism for substrate entry in m -AAA is based on substrate recognition by solvent exposed lateral regions of FtsH cytosolic domain.…”