Andreas Schweitzer, Antje Aufderheide, Till Rudack, Florian Beck, Gunter
Pfeifer, Jurgen M. Plitzko, Eri Sakata, Klaus Schulten, Friedrich Forster,
and Wolfgang Baumeister.
The structure of the human 26S proteasome at a resolution of 3.9
Å.
Proceedings of the National Academy of Sciences, USA,
113:7816-7821, 2016.
(PMC: PMC4948313)
SCHW2016
Protein degradation in eukaryotic cells is performed by the
Ubiquitin-Proteasome System (UPS). The 26S proteasome holocomplex
consists of a core particle (CP) that proteolytically degrades
polyubiquitylated proteins, and a regulatory particle (RP)
containing the AAA-ATPase module. This module controls access
to the proteolytic chamber inside the CP and is surrounded by Non-
ATPase subunits (Rpns) that recognize substrates and deubiquitylate
them prior to unfolding and degradation. The architecture
of the 26S holocomplex is highly conserved between yeast and
humans. The structure of the human 26S holocomplex described
here reveals novel features of the AAA-ATPase heterohexamer.
One subunit, Rpt6, has ADP bound, while the other five have ATP
in their binding pockets. Rpt6 is structurally distinct from the other
five Rpt subunits, most notably in its pore loop region. For Rpns,
the map reveals two main, previously undetected, features: the
C-terminus of Rpn3 protrudes into the mouth of the ATPase ring;
and Rpn1 and Rpn2, the largest proteasome subunits, are linked
by an extended connection. The structural features of the 26S
proteasome observed in this study are likely to be important for
coordinating the proteasomal subunits during substrate processing.
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