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PDBsum entry 2bwe
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Signaling protein
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PDB id
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2bwe
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Contents |
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(+ 0 more)
46 a.a.
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48 a.a.
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(+ 3 more)
48 a.a.
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73 a.a.
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References listed in PDB file
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Key reference
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Title
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Structures of the dsk2 ubl and uba domains and their complex.
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Authors
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E.D.Lowe,
N.Hasan,
J.F.Trempe,
L.Fonso,
M.E.Noble,
J.A.Endicott,
L.N.Johnson,
N.R.Brown.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2006,
62,
177-188.
[DOI no: ]
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PubMed id
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Abstract
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The yeast proteins Dsk2 and Rad23 belong to a family of proteins that contain an
N-terminal ubiquitin-like domain (UBL) and a C-terminal ubiquitin-associated
domain (UBA). Both Dsk2 and Rad23 function as adaptors to target
ubiquitin-labelled proteins to the proteasome through recognition of
polyubiquitin (four or more K48-linked ubiquitins) by their UBA domains and to
the yeast proteasomal subunit Rpn1 by their UBL domains. The crystal structures
of the Dsk2 UBL domain, the Dsk2 UBA domain and the Dsk2 UBA-UBL complex are
reported. In the crystal, the Dsk2 UBA domains associate through electrostatic
interactions to form ninefold helical ribbons that leave the ubiquitin-binding
surface exposed. The UBA-UBL complex explains the reduced affinity of the UBA
domain for UBL compared with ubiquitin and has implications for the regulation
of Dsk2 adaptor function during ubiquitin-mediated proteasomal targeting. A
model is discussed in which two or more Dsk2 UBA molecules may selectively bind
to K48-linked polyubiquitin.
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Figure 5.
Contacts at the UBA-UBL interface. (a) Schematic representation of UBL (cyan) and UBA
(green) showing the contact regions between UBA residues from the end of [alpha] 1
helix, the [alpha] 1/ [alpha] 2 loop and the [alpha] 3 helix with residues
from UBL from the [beta] 3, [beta] 4 and [beta] 5 strands. (b) Details of
the contacts using the same colouring scheme as in (a). All residues from UBA and UBL that
make contacts of <4.5 Å are shown. These are UBA residues D341, M342, G343, F344, Q362,
L365, D366, L369 and G371 and UBL residues R43, I45, S47, G48, I50, H69, V71 and K72. The
view is rotated ~ 90° about the vertical axis from (a). (c) The van der Waals surface
of UBL as seen by the UBA molecule with the UBA molecule and interacting residues
superimposed. The hydrophobic potential (Goodford, 1985 [Goodford, P. J. (1985). J.
Med. Chem. 28, 849-858.]-[bluearr.gif] ) of the surface is coloured with the deepest
hydrophobicity yellow, the middle range in magenta and the surface with neutral
hydrophobic potential in grey (J. Gruber & M. E. M. Noble, unpublished work). The surface
has been made partially transparent to reveal the UBL structure and interacting residues.
The UBL structure without the surface is shown on the right. The view is similar to (b)
and 90° from (a). (d) A view 180° from (c) showing the van der Waals surface of UBA as
seen by the UBL molecule, with the UBL molecule and interacting residues superimposed. The
colouring is as in (c). The UBA molecule without the surface is shown on the right.
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Figure 6.
(a) Comparison of the Dsk2 UBA-UBL complex (green and cyan, respectively) with the Dsk2
UBA-Ub complex (magenta and orange, respectively; from Ohno et al., 2005 [Ohno, A.,
Jee, J., Fujiwara, K., Tenno, T., Goda, N., Tochio, H., Kobayashi, H., Horoaki, H. &
Shirakawa, M. (2005). Structure, 13, 521-532.]-[bluearr.gif] ). The major differences
at the interface are at the [beta] 1/ [beta] 2 loop and the [beta] 3/
[beta] 4 loop of UBL and Ub. Further details are described in the text. (b) A
simplified view of the contacts between Ub (gold) and UBA (magenta) (left) and UBL (cyan)
and UBA (green) (right) showing the domains in the same orientation as Fig. 6
[link]-[turqarr.gif] (a). Only the most significant contacts that differ between the
two structures are shown. The Ub-UBA interface has contacts from Ub residues K6 and L8 to
UBA residues which are not made in the UBBL-UBA complex. The UBL-UBA complex has closer
contacts between I45 and I50 with UBA residues L365 and L369 that in the Ub-UBA complex.
Full details of the contacts are given in the supplementary material.
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The above figures are
reprinted
by permission from the IUCr:
Acta Crystallogr D Biol Crystallogr
(2006,
62,
177-188)
copyright 2006.
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