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PDBsum entry 4n7h
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Protein binding
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PDB id
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4n7h
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PDB id:
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Protein binding
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Title:
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Crystal structure of the complex of 3rd ww domain of human nedd4 and 1st ppxy motif of arrdc3
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Structure:
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E3 ubiquitin-protein ligase nedd4. Chain: a. Fragment: 3rd ww domain (unp residues 840-872). Synonym: cell proliferation-inducing gene 53 protein, neural precursor cell expressed developmentally down-regulated protein 4, nedd-4. Engineered: yes. Arrestin domain-containing protein 3. Chain: b.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: kiaa0093, nedd4, nedd4-1, pig53. Expressed in: escherichia coli. Expression_system_taxid: 469008. Synthetic: yes. Organism_taxid: 9606
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Resolution:
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1.70Å
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R-factor:
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0.191
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R-free:
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0.233
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Authors:
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S.Qi,M.O'Hayre,J.S.Gutkind,J.Hurley
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Key ref:
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S.Qi
et al.
(2014).
Structural and biochemical basis for ubiquitin ligase recruitment by arrestin-related domain-containing protein-3 (ARRDC3).
J Biol Chem,
289,
4743-4752.
PubMed id:
DOI:
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Date:
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15-Oct-13
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Release date:
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08-Jan-14
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PROCHECK
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Headers
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References
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P46934
(NEDD4_HUMAN) -
E3 ubiquitin-protein ligase NEDD4 from Homo sapiens
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Seq:
Struc:
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1319 a.a.
33 a.a.
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Enzyme class:
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E.C.2.3.2.26
- HECT-type E3 ubiquitin transferase.
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Reaction:
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S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6- ubiquitinyl-[acceptor protein]-L-lysine
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DOI no:
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J Biol Chem
289:4743-4752
(2014)
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PubMed id:
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Structural and biochemical basis for ubiquitin ligase recruitment by arrestin-related domain-containing protein-3 (ARRDC3).
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S.Qi,
M.O'Hayre,
J.S.Gutkind,
J.H.Hurley.
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ABSTRACT
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After protracted stimulation, the β2-adrenergic receptor and many other
G-protein-coupled receptors are ubiquitinated and down-regulated.
Arrestin-related domain-containing protein-3 (ARRDC3) has been proposed to
recruit the ubiquitin ligase Nedd4 to the β2-adrenergic receptor. ARRDC3
contains two PPXY motifs that could potentially interact with any of the four WW
domains of Nedd4. Here we dissect the interaction determinants. ARRDC3
PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 μm for
the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3.
Structures of the uncomplexed and PPXY1-bound WW3 domain were determined at 1.1
and 1.7 Å resolution. The structures revealed conformational changes upon
binding and the hydrogen bonding network in exquisite detail. Tight packing of
ARRDC3 Val-352', part of a 310 helix at the C terminus of PPXY1, is important
for high affinity binding to WW3. Although no single WW domain is strictly
essential for the binding of Nedd4 and ARRDC3 expressed in HEK293 cells, high
affinity binding of full-length ARRDC3 and Nedd4 is driven by the avid
interaction of both PPXY motifs with either the WW2-WW3 or WW3-WW4 combinations,
with Kd values as low as 300 nm.
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Links
