The axial channel of the 20S proteasome opens upon binding of the PA200 activator - PubMed (original) (raw)
. 2005 Mar 11;346(5):1221-7.
doi: 10.1016/j.jmb.2004.12.049. Epub 2005 Jan 26.
Affiliations
- PMID: 15713476
- DOI: 10.1016/j.jmb.2004.12.049
The axial channel of the 20S proteasome opens upon binding of the PA200 activator
Joaquin Ortega et al. J Mol Biol. 2005.
Abstract
Proteasomes consist of a proteolytic core called the 20 S particle and ancillary factors that regulate its activity in various ways. PA200 has been identified as a large (200 kDa) nuclear protein that stimulates proteasomal hydrolysis of peptides. To characterize its interaction with the 20 S core, we have visualized PA200-20 S complexes by electron microscopy. Monomers of PA200 bind to one or both ends of the 20 S core. Reconstructed in three dimensions to 23 A resolution from cryo-electron micrographs of the singly bound complex, PA200 has an asymmetric dome-like structure with major and minor lobes. Taking into account previous bioinformatic analysis, it is likely to represent an irregular folding of an alpha-helical solenoid composed of HEAT-like repeats. PA200 makes contact with all alpha-subunits except alpha7, and this interaction induces an opening of the axial channel through the alpha-ring. Thus, the activation mechanism of PA200 is expressed via its allosteric effects on the 20 S core particle, perhaps facilitating release of digestion products or the entrance of substrates.
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