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Crystal structure of the tricorn protease reveals a protein disassembly line

Abstract

The degradation of cytosolic proteins is carried out predominantly by the proteasome, which generates peptides of 7–9 amino acids long1. These products need further processing. Recently, a proteolytic system was identified in the model organism Thermoplasma acidophilum that performs this processing2,3. The hexameric core protein of this modular system, referred to as tricorn protease, is a 720K protease that is able to assemble further into a giant icosahedral capsid, as determined by electron microscopy4. Here, we present the crystal structure of the tricorn protease at 2.0 Å resolution. The structure reveals a complex mosaic protein whereby five domains combine to form one of six subunits, which further assemble to form the 3-2-symmetric core protein. The structure shows how the individual domains coordinate the specific steps of substrate processing, including channelling of the substrate to, and the product from, the catalytic site. Moreover, the structure shows how accessory protein components might contribute to an even more complex protein machinery that efficiently collects the tricorn-released products.

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Figure 1: Structure of tricorn protease.
Figure 2: The active site of tricorn protease.
Figure 3: Internal view of tricorn protease.

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Acknowledgements

We acknowledge financial support of the Deutsche Forschungsgemeinschaft and of Roche Diagnostics. P. Göttig and R. Ramachandran helped with biochemical analyses. We thank G. Bourenkov and H. Bartunik, and G. Leonard for help with synchrotron data collection at DESY BW6 (Hamburg) and ESRF ID14-4 (Grenoble), respectively.

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Correspondence to Hans Brandstetter.

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The authors declare no competing financial interests.

Additional information

The coordinates of the tricorn protease have been deposited in Protein Data Bank under accession code 1K32.

Supplementary information

Figure 1

(JPG 32.5 KB)

Figure 2

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Table 1

(GIF 30.3 KB)

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Brandstetter, H., Kim, JS., Groll, M. et al. Crystal structure of the tricorn protease reveals a protein disassembly line. Nature 414, 466–470 (2001). https://doi.org/10.1038/35106609

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