TY - JOUR
T1 - Structural basis for the processive protein degradation by tricorn protease
AU - Brandstetter, Hans
AU - Kim, Jeong Sun
AU - Groll, Michael
AU - Göttig, Peter
AU - Huber, Robert
N1 - Funding Information:
We thank Markus Kaiser and Luis Moroder for helpful discussions; Gleb Bourenkov and Hans Bartunik at DESY beamline BW6, and Gordon Leonard at ESRF beamline ID14-4 for help with synchrotron data collection. We are grateful to the Deutsche Forschungsgemeinschaft and Roche Diagnostics for financial support.
PY - 2002/7
Y1 - 2002/7
N2 - 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 Å 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.
AB - 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 Å 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.
UR - http://www.scopus.com/inward/record.url?scp=0036660886&partnerID=8YFLogxK
U2 - 10.1515/BC.2002.127
DO - 10.1515/BC.2002.127
M3 - Article
C2 - 12437101
AN - SCOPUS:0036660886
SN - 1431-6730
VL - 383
SP - 1157
EP - 1165
JO - Biological Chemistry
JF - Biological Chemistry
IS - 7-8
ER -