| Structural highlights
Function
[FTSH_ECOLI] Acts as a processive, ATP-dependent zinc metallopeptidase for both cytoplasmic and membrane proteins. Plays a role in the quality control of integral membrane proteins. Degrades a few membrane proteins that have not been assembled into complexes such as SecY, F(0) ATPase subunit a and YccA, and also cytoplasmic proteins sigma-32, LpxC, KdtA and phage lambda cII protein among others. Degrades membrane proteins in a processive manner starting at either the N- or C-terminus; recognition requires a cytoplasmic tail of about 20 residues with no apparent sequence requirements. It presumably dislocates membrane-spanning and periplasmic segments of the protein into the cytoplasm to degrade them, this probably requires ATP. Degrades C-terminal-tagged cytoplasmic proteins which are tagged with an 11-amino-acid nonpolar destabilizing tail via a mechanism involving the 10SA (SsrA) stable RNA.[1] [2] [3] [4] As FtsH regulates the levels of both LpxC and KdtA it is required for synthesis of both the protein and lipid components of lipopolysaccharide (LPS).[5] [6] [7] [8]
Publication Abstract from PubMed
Metalloproteases of the AAA (ATPases associated with various cellular activities) family play a crucial role in protein quality control within the cytoplasmic membrane of bacteria and the inner membrane of eukaryotic organelles. These membrane-anchored hexameric enzymes are composed of an N-terminal domain with one or two transmembrane helices, a central AAA ATPase module, and a C-terminal Zn2+-dependent protease. While the latter two domains have been well studied, so far, little is known about the N-terminal regions. Here, in an extensive bioinformatic and structural analysis, we identified three major, non-homologous groups of N-domains in AAA metalloproteases. By far, the largest one is the FtsH-like group of bacteria and eukaryotic organelles. The other two groups are specific to Yme1: one found in plants, fungi, and basal metazoans and the other one found exclusively in animals. Using NMR and crystallography, we determined the subunit structure and hexameric assembly of Escherichiacoli FtsH-N, exhibiting an unusual alpha+beta fold, and the conserved part of fungal Yme1-N from Saccharomyces cerevisiae, revealing a tetratricopeptide repeat fold. Our bioinformatic analysis showed that, uniquely among these proteins, the N-domain of Yme1 from the cnidarian Hydra vulgaris contains both the tetratricopeptide repeat region seen in basal metazoans and a region of homology to the N-domains of animals. Thus, it is a modern-day representative of an intermediate in the evolution of animal Yme1 from basal eukaryotic precursors.
Structure and Evolution of N-domains in AAA Metalloproteases.,Scharfenberg F, Serek-Heuberger J, Coles M, Hartmann MD, Habeck M, Martin J, Lupas AN, Alva V J Mol Biol. 2015 Jan 8. pii: S0022-2836(15)00004-2. doi:, 10.1016/j.jmb.2014.12.024. PMID:25576874[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tomoyasu T, Gamer J, Bukau B, Kanemori M, Mori H, Rutman AJ, Oppenheim AB, Yura T, Yamanaka K, Niki H, et al.. Escherichia coli FtsH is a membrane-bound, ATP-dependent protease which degrades the heat-shock transcription factor sigma 32. EMBO J. 1995 Jun 1;14(11):2551-60. PMID:7781608
- ↑ Kihara A, Akiyama Y, Ito K. FtsH is required for proteolytic elimination of uncomplexed forms of SecY, an essential protein translocase subunit. Proc Natl Acad Sci U S A. 1995 May 9;92(10):4532-6. PMID:7753838
- ↑ Ogura T, Inoue K, Tatsuta T, Suzaki T, Karata K, Young K, Su LH, Fierke CA, Jackman JE, Raetz CR, Coleman J, Tomoyasu T, Matsuzawa H. Balanced biosynthesis of major membrane components through regulated degradation of the committed enzyme of lipid A biosynthesis by the AAA protease FtsH (HflB) in Escherichia coli. Mol Microbiol. 1999 Feb;31(3):833-44. PMID:10048027
- ↑ Katz C, Ron EZ. Dual role of FtsH in regulating lipopolysaccharide biosynthesis in Escherichia coli. J Bacteriol. 2008 Nov;190(21):7117-22. doi: 10.1128/JB.00871-08. Epub 2008 Sep 5. PMID:18776015 doi:http://dx.doi.org/10.1128/JB.00871-08
- ↑ Tomoyasu T, Gamer J, Bukau B, Kanemori M, Mori H, Rutman AJ, Oppenheim AB, Yura T, Yamanaka K, Niki H, et al.. Escherichia coli FtsH is a membrane-bound, ATP-dependent protease which degrades the heat-shock transcription factor sigma 32. EMBO J. 1995 Jun 1;14(11):2551-60. PMID:7781608
- ↑ Kihara A, Akiyama Y, Ito K. FtsH is required for proteolytic elimination of uncomplexed forms of SecY, an essential protein translocase subunit. Proc Natl Acad Sci U S A. 1995 May 9;92(10):4532-6. PMID:7753838
- ↑ Ogura T, Inoue K, Tatsuta T, Suzaki T, Karata K, Young K, Su LH, Fierke CA, Jackman JE, Raetz CR, Coleman J, Tomoyasu T, Matsuzawa H. Balanced biosynthesis of major membrane components through regulated degradation of the committed enzyme of lipid A biosynthesis by the AAA protease FtsH (HflB) in Escherichia coli. Mol Microbiol. 1999 Feb;31(3):833-44. PMID:10048027
- ↑ Katz C, Ron EZ. Dual role of FtsH in regulating lipopolysaccharide biosynthesis in Escherichia coli. J Bacteriol. 2008 Nov;190(21):7117-22. doi: 10.1128/JB.00871-08. Epub 2008 Sep 5. PMID:18776015 doi:http://dx.doi.org/10.1128/JB.00871-08
- ↑ Scharfenberg F, Serek-Heuberger J, Coles M, Hartmann MD, Habeck M, Martin J, Lupas AN, Alva V. Structure and Evolution of N-domains in AAA Metalloproteases. J Mol Biol. 2015 Jan 8. pii: S0022-2836(15)00004-2. doi:, 10.1016/j.jmb.2014.12.024. PMID:25576874 doi:http://dx.doi.org/10.1016/j.jmb.2014.12.024
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