Structural basis for the processive protein degradation by tricorn protease.
Cell survival critically depends on the efficient use of available resources. This includes both the clearance and the recycling of those protein components that have become futile or defective. Several proteins sequentially accomplish this complex task. The proteasome serves as an initial protein shredder and generates peptides of 7-12 amino acids in length. In general, these products are useless burden to the cell and need further processing. A few years ago, a proteolytic system was identified in the model organism Thermoplasma acidophilum which indeed performs this processing [Tamura et al., Science 274 (1996), 1385-1389]. The hexameric core protein of this modular system, referred to as tricorn protease, is a 720 kDa protease which is able to assemble further into a giant icosahedral capsid, as determined by electron microscopy. Recently, we determined the crystal structure of the tricorn core particle at 2.0 A resolution [Brandstetter et al., Nature 414 (2001), 466-469]. Here we describe the structural and mechanistic basis for tricorn's processive degradation mode, including a novel electrostatic substrate-to-product sink, and suggest how further components might interact with the tricorn protease to complete the cellular waste recycling process.
Brandstetter
Hans
H
Abteilung Strukturforschung, Max-Planck-Institut für Biochemie, Martinsried, Germany.
Kim
Jeong-Sun
JS
Groll
Michael
M
Göttig
Peter
P
Huber
Robert
R
D019843:Archaeal Proteins; D020134:Catalytic Domain; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D010450:Endopeptidases / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation; D055672:Static Electricity; D013822:Thermoplasma / Q000201:enzymology
D019843:Archaeal Proteins; D010450:Endopeptidases; C102094:tricorn protease