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Figure 3.
Figure 3. Structure of a SUMO binding motif mimic bound to
Smt3p–Ubc9p: structural conservation of non-covalent
ubiquitin-like protein–E2 complexes as platforms for
interactions within Ubl pathways. (a) Two complexes as in the
crystal, where Smt3p (yellow)–Ubc9p (cyan) and Smt3p'
(magenta)–Ubc9p' (blue) are related by crystallographic C2
symmetry, showing the uncleaved thrombin-site linker sequence
from the adjacent, crystallographic symmetry-related Smt3p'
packing in a groove in Smt3p. The linker from Smt3p extends five
additional residues beyond the *. (b) Structure of a
SUMO-binding motif mimic bound to Smt3p–Ubc9p. A portion of
the linker from the adjacent, crystallographic symmetry-related
Smt3p' is shown in magenta sticks, as it interacts with the
Smt3p (yellow)–Ubc9p (cyan) complex. The N and C-terminal
regions of the displayed portion of the linker are labeled to
indicate directionality of the peptide-like interaction with
Smt3p. Oxygen atoms are colored red, nitrogen atoms blue, and
Ubc9p's catalytic Cys93 is marked with a green sphere. Hydrogen
bonds and salt-bridges are represented with dashes. (c)
Structures of human SUMO-1 (yellow) in complex with the SBM
regions (magenta) from Nup358/RanBP2,^26 thymine DNA
glycosylase,^33 and PIASX^21 are shown from left to right,
oriented after superposition of SUMO-1 with Smt3p as in (b). The
N and C-terminal regions of the displayed peptide-like regions
of Nup358/RanBP2 and thymine DNA glycosylase, and the peptide
from PIASX, to indicate directionality of the polypeptide
interaction with SUMO-1. Oxygen atoms are colored red, and
nitrogen atoms blue. Hydrogen bonds and salt-bridges are
represented with dashes. (d) Close-up view of interactions
between Smt3p and the uncleaved thrombin-site linker sequence
from the adjacent, crystallographic symmetry-related Smt3p'.
Smt3p is shown in yellow with black labels, and the SBM
mimicking linker in magenta. Oxygen atoms are colored red, and
nitrogen atoms blue. Hydrogen bonds are represented with dashes.
(e) Structure-based sequence alignments of the
SUMO/Smt3p-binding sequences from Nup358/RanBP2, thymine DNA
glycosylase (TDG), PIASX, and the SUMO-binding motif mimic from
the uncleaved thrombin-site linker sequence upstream of Smt3p'
residues used for crystallization (linker). Residues mediating
key hydrophobic interactions are boxed. (f) Structure of the
human ubiquitin (yellow)–UbcH5 (cyan) non-covalent complex,
showing non-covalent interactions between ubiquitin and a
ubiquitin E2 involved in BRCA1-mediated polyubiquitin chain
assembly.^40 This complex is oriented with UbcH5 in the same
position as Ubc9p in (b), after superposition of UbcH5 from the
complex with ubiquitin onto the structure of Ubc9p from
Smt3p–Ubc9p. (g) Structure of the human ubiquitin
(yellow)–MMS2 (cyan) complex, showing non-covalent
interactions between ubiquitin and a non-catalytic E2 variant
involved in Lys63-linked polyubiquitin chain assembly.^40 This
complex is oriented with MMS2 in the same position as Ubc9p in
(b), after superposition of MMS2 from the complex with ubiquitin
onto the structure of Ubc9p from Smt3p–Ubc9p.
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