1LZW: Structural basis of ClpS-mediated switch in ClpA substrate recognition

In Escherichia coli, protein degradation is performed by several proteolytic machines, including ClpAP. Generally, the substrate specificity of these machines is determined by chaperone components, such as ClpA. In some cases, however, the specificity is modified by adaptor proteins, such as ClpS. Here we report the 2.5 A resolution crystal structure of ClpS in complex with the N-terminal domain of ClpA. Using mutagenesis, we demonstrate that two contact residues (Glu79 and Lys 84) are essential not only for ClpAS complex formation but also for ClpAPS-mediated substrate degradation. The corresponding residues are absent in the chaperone ClpB, providing a structural rationale for the unique specificity shown by ClpS despite the high overall similarity between ClpA and ClpB. To determine the location of ClpS within the ClpA hexamer, we modeled the N-terminal domain of ClpA onto a structurally defined, homologous AAA+ protein. From this model, we proposed a molecular mechanism to explain the ClpS-mediated switch in ClpA substrate specificity.
PDB ID: 1LZWDownload
MMDB ID: 21190
PDB Deposition Date: 2002/6/11
Updated in MMDB: 2002/12
Experimental Method:
x-ray diffraction
Resolution: 2.5  Å
Source Organism:
Similar Structures:
Biological Unit for 1LZW: dimeric; determined by author and by software (PISA)
Molecular Components in 1LZW
Label Count Molecule
Proteins (2 molecules)
Protein Ylja(Gene symbol: clpS)
Molecule annotation
Atp-dependent CLP Protease Atp-binding Subunit Clpa(Gene symbol: clpA)
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB