 |
PDBsum entry 3cvr
|
|
|
|
References listed in PDB file
|
 |
|
Key reference
|
|
|
Title
|
|
Structure of a shigella effector reveals a new class of ubiquitin ligases.
|
|
|
Authors
|
|
Y.Zhu,
H.Li,
L.Hu,
J.Wang,
Y.Zhou,
Z.Pang,
L.Liu,
F.Shao.
|
|
|
Ref.
|
|
Nat Struct Biol, 2008,
15,
1302-1308.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Bacterial pathogens have evolved effector proteins with ubiquitin E3 ligase
activities through structural mimicking. Here we report the crystal structure of
the Shigella flexneri type III effector IpaH3, a member of the leucine-rich
repeat (LRR)-containing bacterial E3 family. The LRR domain is structurally
similar to Yersinia pestis YopM and potentially binds to substrates. The
structure of the C-terminal E3 domain differs from the typical RING- and
HECT-type E3s. IpaH3 synthesizes a Lys48-linked ubiquitin chain, and the
reaction requires noncovalent binding between ubiquitin and a specific E2,
UbcH5. Free ubiquitin serves as an acceptor for IpaH3-catalyzed ubiquitin
transfer. Cys363 within a conserved CXD motif acts as a nucleophile to catalyze
ubiquitin transfer through a transthiolation reaction. The D365N mutant is
devoid of E3 activities but turns into a potent ubiquitin-E2 thioesterase. Our
analysis establishes a structurally and mechanistically distinct class of
ubiquitin ligases found exclusively in pathogenic or symbiotic bacteria.
|
|
|
|
|
|
|
|
Figure 2.
(a) Stereo view of the overall structure of full-length
IpaH3. The structure consists of two domains: the N-terminal
leucine-rich repeat (LRR) domain (gold) and the C-terminal
helical domain (green) with the E3 ligase activity. Secondary
structures are marked with numbered labels, and broken lines
indicate disordered loop regions. (b) Secondary-structure
organization and amino acid compositions of the nine LRR motifs
in IpaH3. Secondary-structural elements are depicted along and
above the sequence. The consensus sequences of LRR1–LRR7 are
highlighted in green and the YopM sequence is listed underneath
for comparison. (c) Backbone superimposition of the structures
of YopM (blue; PDB 1JL5) and the LRR domain of IpaH3 (gold).
|
|
Figure 3.
(a) Structure of the C-terminal E3 ligase domain of IpaH3.
Secondary structures are marked with numbered labels, and broken
lines indicate disordered loop regions. Cys363 and Asp365, which
are important for catalyzing ubiquitin transfer, are highlighted
in yellow and shown in sticks. (b) Representative structures of
RING-finger and U-box E3 ligases. The RING-finger and U-box
domains were selected from RING-type E3 ligase Cbl (PDB 1FBV)
and U-box E3 ligase Ufd2p (PDB 2QIZ), respectively. The zinc
ions in Cbl are colored orange. (c) Structure of the HECT domain
of E6AP (PDB 1D5F). The N and C lobes are colored red and
purple, respectively. The catalytic cysteine (Cys820) and the
hinge loop connecting the two lobes are indicated.
|
|
|
|
|
|
The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2008,
15,
1302-1308)
copyright 2008.
|
|
|
|
|
|
|
