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A degradation signal recognition in prokaryotes

Journal of Synchrotron Radiation (2008) 15(3) 246-249
DOI: 10.1107/S0909049507062826
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Abstract

The degradation of ssrA-tagged substrates in prokaryotes is conducted by a subset of ATP-dependent proteases, including ClpXP complex. More than 630 sequences of ssrA have been identified from 514 species, and are conserved in a wide range of prokaryotes. SspB protein markedly stimulates the degradation of these ssrA-tagged substrates by the ClpXP proteolytic machine. The dimeric SspB protein is composed of a compact ssrA-binding domain, which has a dimerization surface and a flexible C-terminal tail with a ClpX-binding motif at its very end. Since SspB is an adaptor protein for the ClpXP complex, designed mutagenesis, fluorescence spectroscopy, biochemistry and X-ray crystallography have been used to investigate the mechanism of delivery of ssrA-tagged proteins. In this paper the structural basis of ssrA-tag recognition by ClpX and SspB, as well as SspB-tail recognition by ZBD, is described. © 2008 International Union of Crystallography Printed in Singapore - All rights reserved.

Figures

  • Figure 1 Schematic model of the full-length ClpX hexamer. A monomeric model of the ATPase domain of E. coli ClpX has been generated with that of H. pylori ClpX [Protein Data Bank (PDB) ID: 1UM8] using the SWISS-MODEL server (Schwede et al., 2003) initially. The hexameric model has been generated with the guidance of HslU hexamer (PDB ID: 1E94), and the resulting model was energetically minimized using CNS software (Brunger et al., 1998). Although the exact orientation of ZBD is ambiguous, their location is distal to the ATPase domain (AAA+ ring) of ClpX based on earlier electron microscopic images (Grimaud et al., 1998), as well as the direction of each chain terminus (N-terminus for the polypeptide chain of ATPase domain and C-terminus for that of ZBD). (a) Top view showing the hexameric pore in the center. The ZBD is drawn with ribbon and the ATPase domain (AAA) with ribbon plus transparent molecular surface, and the linker between the ATPase domain and ZBD is missing. (b) Side view [90 rotation of (a) along the horizontal axis] with the ZBD domain extending upward. The figure was drawn using PyMOL (http://www.pymol.org).
  • Figure 2 (a) Recognition determinants in the ssrA tag for ClpX (coloured red), SspB (green) and ClpA (blue). (b) Recognition determinants in the SspB tail for ZBD of ClpX and the conserved ZBD-interacting determinants in the ClpX interacting proteins, RssB and UmuD. Leucine residues (coloured red) are the key determinant. Other residues (pink) in SspB are also involved in the interaction with ZBD. (c) Structure of the SspB-ssrA complex. Ribbon diagram with transparent surface of dimeric SspB and stick model of ssrA peptides. The flexible C-terminal tail of SspB is invisible in the crystal structure (PDB ID: 1OX9). (d) Structure of ZBD-XB complex. Ribbon diagram with transparent surface of dimeric ZBD and stick model of SspB-tail peptides (PDB ID: 2DS8). The two slate-coloured balls are bound zinc atoms. The orientation of (c) and (d) is a view looking down at the twofold molecular symmetry. Parts (c) and (d) were also drawn using PyMOL.
  • Figure 3 Schematic drawing of ClpX. The monomeric ATPase domain of ClpX is represented as a piece of the hexagonal casket at the bottom. The monomeric Nterminal ZBD is a cylinder at the top. Each ZBD monomer contains a binding site for the SspB tail based on the crystal structure. Therefore, the purple-coloured pairs are all possible functional ZBD units for efficient delivery of ssrA-tagged substrates by SspB adaptor protein (a)–(d).

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APA

Park, E. Y., & Song, H. K. (2008). A degradation signal recognition in prokaryotes. Journal of Synchrotron Radiation, 15(3), 246–249. https://doi.org/10.1107/S0909049507062826

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