 |
PDBsum entry 2oz4
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Cell adhesion
|
PDB id
|
|
|
|
2oz4
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
265 a.a.
|
|
|
|
|
|
|
|
|
|
|
214 a.a.
|
|
|
|
|
|
|
|
|
|
|
208 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structural plasticity in ig superfamily domain 4 of icam-1 mediates cell surface dimerization.
|
|
|
Authors
|
|
X.Chen,
T.D.Kim,
C.V.Carman,
L.Z.Mi,
G.Song,
T.A.Springer.
|
|
|
Ref.
|
|
Proc Natl Acad Sci U S A, 2007,
104,
15358-15363.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The Ig superfamily (IgSF) intercellular adhesion molecule-1 (ICAM-1)
equilibrates between monomeric and dimeric forms on the cell surface, and
dimerization enhances cell adhesion. A crystal structure of ICAM-1 IgSF domains
(D) 3-5 revealed a unique dimerization interface in which D4s of two protomers
fuse through edge beta-strands to form a single super beta-sandwich domain.
Here, we describe a crystal structure at 2.7-A resolution of monomeric ICAM-1
D3-D5, stabilized by the monomer-specific Fab CA7. CA7 binds to D5 in a region
that is buried in the dimeric interface and is distal from the dimerization site
in D4. In monomeric ICAM-1 D3-D5, a 16-residue loop in D4 that is disordered in
the dimeric structure could clearly be traced as a BC loop, a short C strand,
and a CE meander with a cis-Pro followed by a solvent-exposed, flexible
four-residue region. Deletions of 6 or 10 residues showed that the C-strand is
essential for monomer stability, whereas a distinct six-residue deletion showed
little contribution of the CE meander. Mutation of two inward-pointing Leu
residues in edge beta-strand E to Lys increased monomer stability, confirming
the hypothesis that inward-pointing charged side chains on edge beta-strands are
an important design feature to prevent beta-supersheet formation. Overall, the
studies reveal that monomer-dimer transition is associated with a surprisingly
large, physiologically relevant, IgSF domain rearrangement.
|
|
|
|
|
|
|
|
Figure 3.
Fig. 3. Structural properties of D4. (A) Backbone C^  trace of
D4 colored in rainbow from highest (red) to lowest (blue) B
factor. Atoms of cis-Pro-319 and atoms C and O of Val-318 are
represented with sticks, and the hydrogen bond in the turn
between the C-strand and CE meander is dashed. The disulfide
bond is shown in yellow. (B) Comparison of the CE edges of D2
(magenta) and monomeric D4 (cyan) of ICAM-1. Superposition is on
 -strands B, C, E, and F
and the region containing -strands A, A', and G is
omitted for clarity.
|
|
Figure 4.
Fig. 4. The CA7 Fab binding site in D5. CA7 Fab is shown as
a surface representation colored in wheat (heavy chain) and
light blue (light chain) bound to monomeric D5 shown as a
magenta ribbon, with indicated side chains in the AA loop at the
center of the epitope as black sticks. Dimeric D4 and D5 are
shown as ribbons with a cyan monomer and a yellow monomer
superimposed on monomeric D5. The inward-pointing Leu residues
of -strand E of the cyan
monomer are shown as blue sticks.
|
|
|
|
|
|
|
|
|
|
