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PDBsum entry 2i1j
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Cell adhesion, membrane protein
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PDB id
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2i1j
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References listed in PDB file
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Key reference
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Title
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Self-Masking in an intact erm-Merlin protein: an active role for the central alpha-Helical domain.
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Authors
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Q.Li,
M.R.Nance,
R.Kulikauskas,
K.Nyberg,
R.Fehon,
P.A.Karplus,
A.Bretscher,
J.J.Tesmer.
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Ref.
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J Mol Biol, 2007,
365,
1446-1459.
[DOI no: ]
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PubMed id
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Abstract
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Ezrin/radixin/moesin (ERM) family members provide a regulated link between the
cortical actin cytoskeleton and the plasma membrane to govern membrane structure
and organization. Here, we report the crystal structure of intact insect moesin,
revealing that its essential yet previously uncharacterized alpha-helical domain
forms extensive interactions with conserved surfaces of the band
four-point-one/ezrin/radixin/moesin (FERM) domain. These interdomain contacts
provide a functional explanation for how PIP(2) binding and tyrosine
phosphorylation of ezrin lead to activation, and provide an understanding of
previously enigmatic loss-of-function missense mutations in the tumor suppressor
merlin. Sequence conservation and biochemical results indicate that this
structure represents a complete model for the closed state of all ERM-merlin
proteins, wherein the central alpha-helical domain is an active participant in
an extensive set of inhibitory interactions that can be unmasked, in a
rheostat-like manner, by coincident regulatory factors that help determine cell
polarity and membrane structure.
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Figure 2.
Figure 2. Comparison of dormant human and Sfmoesin structures.
(a) The human FERM–C-terminal domain complex (PDB code 1EF1).
The three lobes of the ERM domain (F1, F2 and F3) are colored
cyan and the C-terminal domain is colored red. The β1 strand
of the C-terminal domain is contributed by a crystal-packing
interaction. (b) The 2.1 Å Sfmoesin structure. The
α-helical domain (yellow) folds into three extended helices
(αA, αB and αC), each containing elements that pack against
the FERM domain. The αB and αC helices form an anti-parallel
coiled-coil. (c) In the 3.0 Å structure, 67 more residues
of the  vert,
similar 70 Å αB/αC coiled-coil are revealed. Figure
2. Comparison of dormant human and Sfmoesin structures. (a) The
human FERM–C-terminal domain complex (PDB code 1EF1). The
three lobes of the ERM domain (F1, F2 and F3) are colored cyan
and the C-terminal domain is colored red. The β1 strand of the
C-terminal domain is contributed by a crystal-packing
interaction. (b) The 2.1 Å Sfmoesin structure. The
α-helical domain (yellow) folds into three extended helices
(αA, αB and αC), each containing elements that pack against
the FERM domain. The αB and αC helices form an anti-parallel
coiled-coil. (c) In the 3.0 Å structure, 67 more residues
of the [3]not, vert, similar 70 Å αB/αC coiled-coil are
revealed.
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Figure 4.
Figure 4. Extent and sequence conservation of the surfaces
buried by the α-helical domain and linker region. (a) The
Sfmoesin FERM domain. The view is rotated by vert,
similar 180° around a vertical axis from that in Figure 2.
(b) Molecular surface of the FERM domain. Yellow regions are
those in contact with the α-helical domain and linker region (
vert,
similar 1800 Å^2 of buried accessible surface area). (c)
Conservation of the FERM domain. Magenta regions correspond to
residues that are either identical or substituted conservatively
(e.g. Asp/Glu, Arg/Lys, Ser/Thr) in all ERM-merlin proteins.
Green regions correspond to residues conserved only in the ERM
family. Figure 4. Extent and sequence conservation of the
surfaces buried by the α-helical domain and linker region. (a)
The Sfmoesin FERM domain. The view is rotated by [3]not, vert,
similar 180° around a vertical axis from that in [4]Figure
2. (b) Molecular surface of the FERM domain. Yellow regions are
those in contact with the α-helical domain and linker region (
[5]not, vert, similar 1800 Å^2 of buried accessible
surface area). (c) Conservation of the FERM domain. Magenta
regions correspond to residues that are either identical or
substituted conservatively (e.g. Asp/Glu, Arg/Lys, Ser/Thr) in
all ERM-merlin proteins. Green regions correspond to residues
conserved only in the ERM family.
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The above figures are
reprinted
from an Open Access publication published by Elsevier:
J Mol Biol
(2007,
365,
1446-1459)
copyright 2007.
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