Structure and Evolution of N-domains in AAA Metalloproteases. Issue 4 (27th February 2015)

• Record Type: Journal Article
• Authors: Scharfenberg, Franka; Serek-Heuberger, Justyna; Coles, Murray; Hartmann, Marcus D.; Habeck, Michael; Martin, Jörg; Lupas, Andrei N.; Alva, Vikram
• Is Part Of: Journal of molecular biology. Volume 427:Issue 4(2015:Feb. 15)
• Page Start: 910
• Page End: 923
• Publication Date: 2015-02-27
• Subjects: TPR tetratricopeptide repeat -- TM transmembrane -- 2D two dimensional -- 3D three-dimensional -- PDB Protein Data Bank -- EM electron microscopy -- NOESY nuclear Overhauser enhancement spectroscopy -- NCBI National Center for Biotechnology Information -- HMM hidden Markov model; AAA proteins -- FtsH -- Yme1 -- m-AAA -- i-AAA; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2014.12.024
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: Metalloproteases of the AAA ( A TPases a ssociated with various cellular a ctivities) 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 Zn 2 + -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 Escherichia coli FtsH-N, exhibiting an unusual α + β 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. Graphical Abstract: Highlights: Three major, distinct groups of AAA metalloprotease N-domains are found. Structures of E . coli FtsH-N and yeast Yme1-N are reported. Yme1 of cnidarians has an evolutionarily intermediate architecture to animal Yme1.