 |
PDBsum entry 1pvh
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Signaling protein/cytokine
|
PDB id
|
|
|
|
1pvh
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Convergent mechanisms for recognition of divergent cytokines by the shared signaling receptor gp130.
|
|
|
Authors
|
|
M.J.Boulanger,
A.J.Bankovich,
T.Kortemme,
D.Baker,
K.C.Garcia.
|
|
|
Ref.
|
|
Mol Cell, 2003,
12,
577-589.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Gp130 is a shared cell-surface signaling receptor for at least ten different
hematopoietic cytokines, but the basis of its degenerate recognition properties
is unknown. We have determined the crystal structure of human leukemia
inhibitory factor (LIF) bound to the cytokine binding region (CHR) of gp130 at
2.5 A resolution. Strikingly, we find that the shared binding site on gp130 has
an entirely rigid core, while the LIF binding interface diverges sharply in
structure and chemistry from that of other gp130 ligands. Dissection of the
LIF-gp130 interface, along with comparative studies of other gp130 cytokines,
reveal that gp130 has evolved a "thermodynamic plasticity" that is
relatively insensitive to ligand structure, to enable crossreactivity. These
observations reveal a novel and alternative mechanism for degenerate recognition
from that of structural plasticity.
|
|
|
|
|
|
|
|
Figure 2.
Figure 2. Structural Topology of the LIF/gp130 D2D3 Crystal
Structure(A) Backbone structure as viewed from the side of the
LIF/gp130 complex.(B) Close-up view of the interface showing
four clear spheres of electron density (green) calculated at 2.5
σ from an omit map representing buried solvent molecules.(C)
“Top” view of the LIF/gp130 complex showing LIF bound to
gp130 through its N-terminal region and the N-terminal flap.(D)
Close-up view of omit map electron density contoured at 2.5 σ
showing the well-ordered N-terminal flap. Molscript (Kraulis,
1991) and Raster3D (Merritt and Murphy, 1994) were used to
prepare secondary structure figures and Bobscript (Esnouf, 1997)
was used to prepare electron density figures.
|
|
Figure 5.
Figure 5. Surface Representations Showing the Site III
Interfaces of LIF OSM, IL-6, and Viral IL-6The site III LIF and
OSM, which engage LIF receptor (LIFR) is defined by both a
conserved phenylalanine and a lysine residue. The structural
paradigm for site III has been established with hIL-6 (Boulanger
et al., 2003) and viral IL-6 (Chow et al., 2001), where the hot
spot residue is a single tryptophan that engages the Ig domain
of gp130.
|
|
|
|
|
|
The above figures are
reprinted
by permission from Cell Press:
Mol Cell
(2003,
12,
577-589)
copyright 2003.
|
|
|
|
|
|
|
