PDBsum entry 1um8

Chaperone

PDB id: 1um8

Contents

Protein chain

327 a.a. *

Ligands

ADP

Waters ×85

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Crystal structure of clpx molecular chaperone from helicobacter pylori.

Authors

D.Y.Kim, K.K.Kim.

Ref.

J Biol Chem, 2003, 278, 50664-50670. [DOI no: 10.1074/jbc.M305882200]

PubMed id

14514695

Abstract

ClpX, a heat shock protein 100 chaperone, which acts as the regulatory subunit of the ATP-dependent ClpXP protease, is responsible for intracellular protein remodeling and degradation. To provide a structural basis for a better understanding of the function of the Clp ATPase family, the crystal structures of Helicobacter pylori ClpX, lacking an N-terminal Cys cluster region complexed with ADP, was determined. The overall structure of ClpX is similar to that of heat shock locus U (HslU), consisting of two subdomains, with ADP bound at the subdomain interface. The crystal structure of ClpX reveals that a conserved tripeptide (LGF) is located on the tip of ClpP binding loop extending from the N-terminal subdomain. A hexameric model of ClpX suggests that six tripeptides make hydrophobic contacts with the hydrophobic clefts of the ClpP heptmer asymmetrically. In addition, the nucleotide binding environment provides the structural explanation for the hexameric assembly and the modulation of ATPase activity.

Figure 1.
FIG. 1. The structures of Hp ClpX-ASD, E. coli HslU, and E. coli ClpA D2. A, the overall structure of Hp ClpX-ASD is presented as a ribbon diagram. The ATPase core domain, SSD domain, and LGF tripeptide are colored magenta, green, and red, respectively. The ATP molecule is shown in orange as a ball-and-stick model. Each secondary structure and the N and C termini are labeled. The protease interface and substrate interface are indicated in the figure to display the relative orientation of Hp ClpX. E. coli HslU (B) and E. coli ClpA D2 (C), positioned in the same orientation with Hp ClpX-ASD, are displayed as ribbon diagrams, with the same color codes. D, the sequences of Hp ClpX, E. coli ClpX, and E. coli HslU were aligned by the CLUSTALW program (28), following the manual adjustment based on a structural comparison. The secondary structures of Hp ClpX-ASD are indicated by a cylinder for the -helix and an arrow for the -strand. The amino acids in the LGF peptide are boxed in blue. In the alignment, identical residues are boxed in red, with homologous residues boxed in yellow.

Figure 2.
FIG. 2. The hexamer model of Hp ClpX-ASD and E. coli ClpP heptamer. The ribbon diagrams of the hexamer model of Hp ClpX-ASD viewed along the 6-fold axis from the protease interface (A) and from the side (B) are shown. The same color schemes as described in the legend to Fig. 1A are used. However, each subunit is colored with a different brightness. The N and C termini of one subunit are labeled. The surface charge distribution of Hp ClpX-ASD (C) and E. coli ClpP (D) is shown. The protease interface of Hp ClpX and the ATPase interface of ClpP are drawn to show the possible ClpX-ClpP interface. The red and blue areas represent the negatively and positively charged surfaces, respectively. The white region represents the hydrophobic surface. The LGF peptide of ClpX (residues 297, 298, and 299), and the conserved hydrophobic cleft of ClpP (residues 60, 62, 82, 90, 92, 112, 114, and 189), are colored in yellow.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 50664-50670) copyright 2003.