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PDBsum entry 3wa0
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Cell adhesion
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PDB id
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3wa0
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Contents |
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(+ 0 more)
289 a.a.
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11 a.a.
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11 a.a.
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PDB id:
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| Name: |
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Cell adhesion
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Title:
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Crystal structure of merlin complexed with dcaf1/vprbp
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Structure:
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Merlin. Chain: a, b, c, d, e, f. Fragment: unp residues 19-314. Synonym: moesin-ezrin-radixin-like protein, neurofibromin-2, schwannomin. Engineered: yes. Protein vprbp. Chain: g, h. Fragment: unp residues 1417-1506.
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Source:
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Mus musculus. Mouse. Organism_taxid: 10090. Strain: dh5a. Gene: nf2. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human.
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Resolution:
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2.31Å
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R-factor:
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0.237
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R-free:
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0.264
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Authors:
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T.Mori,S.Gotoh,M.Shirakawa,T.Hakoshima
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Key ref:
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T.Mori
et al.
(2014).
Structural basis of DDB1-and-Cullin 4-associated Factor 1 (DCAF1) recognition by merlin/NF2 and its implication in tumorigenesis by CD44-mediated inhibition of merlin suppression of DCAF1 function.
Genes Cells,
19,
603-619.
PubMed id:
DOI:
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Date:
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20-Apr-13
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Release date:
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28-May-14
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PROCHECK
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Headers
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References
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P46662
(MERL_MOUSE) -
Merlin from Mus musculus
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Seq:
Struc:
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596 a.a.
289 a.a.
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Enzyme class:
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Chains G, H:
E.C.2.7.11.1
- non-specific serine/threonine protein kinase.
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Reaction:
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1.
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L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H+
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2.
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L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H+
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L-seryl-[protein]
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+
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ATP
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=
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O-phospho-L-seryl-[protein]
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+
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ADP
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+
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H(+)
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L-threonyl-[protein]
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+
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ATP
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=
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O-phospho-L-threonyl-[protein]
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+
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ADP
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+
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H(+)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Genes Cells
19:603-619
(2014)
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PubMed id:
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Structural basis of DDB1-and-Cullin 4-associated Factor 1 (DCAF1) recognition by merlin/NF2 and its implication in tumorigenesis by CD44-mediated inhibition of merlin suppression of DCAF1 function.
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T.Mori,
S.Gotoh,
M.Shirakawa,
T.Hakoshima.
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ABSTRACT
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Merlin, a tumor suppressor encoded by the neurofibromatosis type 2 gene, has
been shown to suppress tumorigenesis by inhibiting the Cullin 4-RING E3
ubiquitin ligase CRL4(DCAF) (1) in the nucleus. This inhibition is mediated by
direct binding of merlin to DDB1-and-Cullin 4-associated Factor 1 (DCAF1), yet
the binding mode of merlin to DCAF1 is not well defined. Here, we report
structural and biophysical studies of the merlin binding to DCAF1 and its
interference with CD44 binding. The crystal structure of the merlin FERM domain
bound to the DCAF1 C-terminal acidic tail reveals that the hydrophobic IILXLN
motif located at the C-terminal end of DCAF1 binds subdomain C of the FERM
domain by forming a β-strand. The binding site and mode resemble that of merlin
binding to the CD44 cytoplasmic tail. Competition binding assay showed that CD44
and DCAF1 compete for binding to the merlin FERM domain in solution. The CD44
cytoplasmic tail is known to be cleaved for nuclear translocation by regulated
intra-membrane proteolysis (RIP). Our structure implies that, in the nucleus,
the CD44 cytoplasmic tail cleaved by RIP could release DCAF1 from merlin by
competing for binding to the merlin FERM domain, which results in the inhibition
of merlin-mediated suppression of tumorigenesis.
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