 |
PDBsum entry 1nd7
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Conformational flexibility underlies ubiquitin ligation mediated by the wwp1 hect domain e3 ligase.
|
|
|
Authors
|
|
M.A.Verdecia,
C.A.Joazeiro,
N.J.Wells,
J.L.Ferrer,
M.E.Bowman,
T.Hunter,
J.P.Noel.
|
|
|
Ref.
|
|
Mol Cell, 2003,
11,
249-259.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Ubiquitin ligases (E3) select proteins for ubiquitylation, a modification that
directs altered subcellular trafficking and/or degradation of the target
protein. HECT domain E3 ligases not only recognize, but also directly catalyze,
ligation of ubiquitin to their protein substrates. The crystal structure of the
HECT domain of the human ubiquitin ligase WWP1/AIP5 maintains a two-lobed
structure like the HECT domain of the human ubiquitin ligase E6AP. While the
individual N and C lobes of WWP1 possess very similar folds to those of E6AP,
the organization of the two lobes relative to one another is different from E6AP
due to a rotation about a polypeptide hinge linking the N and C lobes.
Mutational analyses suggest that a range of conformations achieved by rotation
about this hinge region is essential for catalytic activity.
|
|
|
|
|
|
|
|
Figure 5.
Figure 5. Stabilizing Interactions at the Base of the Hinge
Loop(A) Residue contacts within E6AP in the L shape
conformation. Lys549 interacts with Asn822, Gln553 hydrogen
bonds with Thr819, and Asp607 appears to interact with
His609.(B) Residue contacts within WWP1/AIP5 in the  shape
conformation. Arg613 interacts with Gly610, and His621 hydrogen
bonds with Asp675. Both pairs of interactions bridge the H3
helix to loop regions (S2/H3 and H4/H5 loops).(C) WWP1/AIP5
(residues 546–922) was used as a reference for wild-type
autoubiquitylation activity.
|
|
Figure 6.
Figure 6. C Lobe and N Lobe Interactions in WWP1/AIP5(A)
Residue contacts between the N and C lobes within WWP1/AIP5 in
the shape
conformation. Asp793 on the N lobe interacts with Arg845 on the
C lobe. Gln848 and Arg855 on the C lobe form hydrogen bonds with
Glu798 and the carbonyl oxygen of Thr676. Asp793 and Arg845 are
highly conserved, and Glu798, Gln848, and Arg855 are absolutely
conserved among 22 HECT domain sequences analyzed (data not
shown).(B) Ubiquitin transfer assays.
|
|
|
|
|
|
The above figures are
reprinted
by permission from Cell Press:
Mol Cell
(2003,
11,
249-259)
copyright 2003.
|
|
|
|
|
|
|
