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PDBsum entry 4zri
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Signaling protein/transferase
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PDB id
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4zri
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PDB id:
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| Name: |
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Signaling protein/transferase
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Title:
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Crystal structure of merlin-ferm and lats2
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Structure:
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Merlin. Chain: a, b. Fragment: ferm domain, unp residues 1-320. Synonym: moesin-ezrin-radixin-like protein,neurofibromin-2, schwannomerlin,schwannomin. Engineered: yes. Serine/threonine-protein kinase lats2. Chain: c, d. Fragment: unp residues 68-99.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: nf2, sch. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: lats2, kpm. Expression_system_taxid: 562
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Resolution:
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2.70Å
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R-factor:
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0.229
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R-free:
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0.270
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Authors:
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F.Li,H.Zhou,J.Long,Y.Shen
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Key ref:
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Y.Li
et al.
(2015).
Angiomotin binding-induced activation of Merlin/NF2 in the Hippo pathway.
Cell Res,
25,
801-817.
PubMed id:
DOI:
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Date:
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12-May-15
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Release date:
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17-Jun-15
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PROCHECK
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Headers
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References
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P35240
(MERL_HUMAN) -
Merlin from Homo sapiens
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Seq:
Struc:
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595 a.a.
293 a.a.
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Enzyme class:
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Chains C, D:
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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Cell Res
25:801-817
(2015)
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PubMed id:
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Angiomotin binding-induced activation of Merlin/NF2 in the Hippo pathway.
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Y.Li,
H.Zhou,
F.Li,
S.W.Chan,
Z.Lin,
Z.Wei,
Z.Yang,
F.Guo,
C.J.Lim,
W.Xing,
Y.Shen,
W.Hong,
J.Long,
M.Zhang.
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ABSTRACT
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The tumor suppressor Merlin/NF2 functions upstream of the core Hippo pathway
kinases Lats1/2 and Mst1/2, as well as the nuclear E3 ubiquitin ligase
CRL4(DCAF1). Numerous mutations of Merlin have been identified in
Neurofibromatosis type 2 and other cancer patients. Despite more than two
decades of research, the upstream regulator of Merlin in the Hippo pathway
remains unknown. Here we show by high-resolution crystal structures that the
Lats1/2-binding site on the Merlin FERM domain is physically blocked by Merlin's
auto-inhibitory tail. Angiomotin binding releases the auto-inhibition and
promotes Merlin's binding to Lats1/2. Phosphorylation of Ser518 outside the
Merlin's auto-inhibitory tail does not obviously alter Merlin's conformation,
but instead prevents angiomotin from binding and thus inhibits Hippo pathway
kinase activation. Cancer-causing mutations clustered in the angiomotin-binding
domain impair angiomotin-mediated Merlin activation. Our findings reveal that
angiomotin and Merlin respectively interface cortical actin filaments and core
kinases in Hippo signaling, and allow construction of a complete Hippo signaling
pathway.
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