ausblenden:
Schlagwörter:
-
Zusammenfassung:
The 26S proteasome is an integral element of the ubiquitin-proteasome
system(UPS) and, as such, responsible for regulated degradation of
proteins in eukaryotic cells.It consists of the core particle, which
catalyzes the proteolysis of substrates into small peptides, and the
regulatory particle, which ensures specificity for a broad range of
substrates.The heart of the regulatory particle is an AAA-ATPase
unfoldase, which is surrounded by non-ATPase subunits enabling substrate
recognition and processing. Cryo-EM-based studies revealed the molecular
architecture of the 26S proteasome and its conformational
rearrangements, providing insights into substrate recognition,
commitment, deubiquitylation and unfolding. The cytosol proteasomal
degradation of polyubiquitylated substrates is tuned by various
associating cofactors, including deubiquitylating enzymes, ubiquitin
ligases,shuttling ubiquitin receptors and the AAA-ATPase Cdc48/p97.
Cdc48/p97 and its cofactors function upstream of the 26S proteasome, and
their modular organization exhibits some striking analogies to the
regulatory particle. In archaea PAN, the closest regulatory particle
homolog and Cdc48 even have overlapping functions, underscoring their
intricate relationship.Here, we review recent insights into the
structure and dynamics of the 26S proteasome and its associated
machinery, as well as our current structural knowledge on the Cdc48/p97
and its cofactors that function in the ubiquitin-proteasome system
(UPS).