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Figure 1.
Fig. 1. Proteasomal proteolytically active sites involved
in the generation of MHC class I ligands. (a) Surface
representation of the yeast 20S proteasome in complex with
propeptides, clipped along the cylindrical pseudo sevenfold
symmetry axis. Accessible surfaces are depicted in blue, and the
cutting surface is in white. Propeptides are shown as
space-filling models in yellow and indicate the proteolytically
different active sites. The various proteolytic active centers
are marked in a specific color coding: blue, subunit  1; red,
subunit 2; and green, subunit
5.
Cleavage preferences, termed caspase-, tryptic-, and
chymotryptic-like activity, are zoomed and illustrated as
surfaces; propeptides are presented as ball-and-stick models.
Surface colors indicate positive and negative electrostatic
potential contoured from 15 kT/e (intense blue) to –15 kT/e
(intense red). (b) Topology of the 28 subunits of the yeast 20S
proteasome in ribbon presentation. IFN-  -inducible mammalian
subunits 1i, 2I, and 5i are
modeled by the corresponding constitutive yeast subunits. (c
Left) MHC class I molecule in complex with an antigen (c Right).
Structural superposition of propeptides 1, 2, and 5 with
NEF-HIV1 and GAG-HIV2 antigen bound to MHC class I molecules.
(d) Standard orientation for peptide substrates bound to the
proteasomal specificity pockets. Substrates are oriented from
their N to their C terminus. The scissile peptide bond is shown
in magenta, flanked by the nucleophilic water molecule, which is
incorporated into the product during hydrolysis. Residues on the
left side of the scissile peptide bond in substrates, generating
the C-terminal part in the product, are termed P sites; residues
on the right side are termed P' sites. Specificity pockets,
which are responsible for ligand stabilization, are termed S and
S' pockets, respectively (11). (e) Sequence alignment of the
yeast and the human constitutive subunit and immunosubunit for
subunit 1 (nonprimed S1 site,
Upper) and subunit 5 (nonprimed S1 and
primed substrate-binding channel, Lower). Conserved residues are
marked by vertical green boxes, significant variations between
human constitutive subunits and immunosubunits are highlighted
by yellow boxes, and variations in residues in proximity to the
specificity pockets are shown against a gray background.
Secondary structure elements are indicated in green.
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