 |
PDBsum entry 1mq9
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Immune system
|
PDB id
|
|
|
|
1mq9
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structures of the alpha l I domain and its complex with icam-1 reveal a shape-Shifting pathway for integrin regulation.
|
|
|
Authors
|
|
M.Shimaoka,
T.Xiao,
J.H.Liu,
Y.Yang,
Y.Dong,
C.D.Jun,
A.Mccormack,
R.Zhang,
A.Joachimiak,
J.Takagi,
J.H.Wang,
T.A.Springer.
|
|
|
Ref.
|
|
Cell, 2003,
112,
99.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The structure of the I domain of integrin alpha L beta 2 bound to the Ig
superfamily ligand ICAM-1 reveals the open ligand binding conformation and the
first example of an integrin-IgSF interface. The I domain Mg2+ directly
coordinates Glu-34 of ICAM-1, and a dramatic swing of I domain residue Glu-241
enables a critical salt bridge. Liganded and unliganded structures for both
high- and intermediate-affinity mutant I domains reveal that ligand binding can
induce conformational change in the alpha L I domain and that allosteric signals
can convert the closed conformation to intermediate or open conformations
without ligand binding. Pulling down on the C-terminal alpha 7 helix with
introduced disulfide bonds ratchets the beta 6-alpha 7 loop into three different
positions in the closed, intermediate, and open conformations, with a
progressive increase in affinity.
|
|
|
|
|
|
|
|
Figure 1.
Figure 1. Two αL I Domains Bound to an ICAM-1 Dimer(A)
Ribbon diagram of one monomeric unit of the
intermediate-affinity αL I domain (gold) complex with ICAM-1
domains 1-2 (cyan). The Mg^2+ ion is shown as a magenta sphere.
I domain MIDAS and ICAM-1 Glu-34 side chains are shown as
ball-and-stick with red oxygen atoms. The interacting β strands
C, D, and F of ICAM-1 are labeled. N-acetyl glucosamine residues
of ICAM-1 are shown with silver bonds.(B) The two ICAM-1-I
domain complexes in the crystallographic asymmetric unit are
shown with the I domains colored gold and the two ICAM-1
molecules colored cyan and green. The 2-fold axis between the
ICAM-1 molecules is in the vertical direction, normal to the
predicted membrane plane. Positions of the magnesium ions
(magenta spheres) and Glu-34 of ICAM-1 (CPK) are shown for
reference. The ICAM-1 Val-51 residues at the center of the
ICAM-1 dimer interface are shown as gray CPK models.(C) A view
of domains 1 of the ICAM-1 dimer (cyan and green), rotated about
90° from the view in (B), with domain 1 of the uncomplexed
ICAM-1 molecule A dimer (Casasnovas et al., 1998) superimposed
using domain 1 of one of the ICAM-1 molecules (black), whereas
the other one is colored gray. Figures 1–5 are prepared with
programs GLR (provided by L. Esser), Molscript (Kraulis, 1991),
Bobscript (Esnouf, 1997), Raster3D (Merritt and Murphy, 1994),
GRASP (Nicholls et al., 1991), and Povray (The Povray Team,
http://www.povray.org).
|
|
Figure 3.
Figure 3. MIDAS StructuresStructures are from the I
domain:ICAM-1 complex (A), the pseudo-liganded high-affinity I
domain (B), the unliganded high-affinity I domain (C), the
unliganded intermediate-affinity I domain (D), and the wild-type
I domain (E) (1LFA) (Qu and Leahy, 1996). The keys to the color
scheme are shown below, with the ICAM-1 or ligand mimetic
molecule colored cyan in (A) and (B). The metal ions are colored
blue, water molecule and ligating side chain oxygen atoms are
colored red, and the chloride ion from the wild-type I domain
structure is colored orange. The MIDAS residues and Glu-34 from
ICAM-1 in (A) and Glu-272 from a lattice mate I domain in (B)
are shown as ball-and-stick models. Metal coordination and
hydrogen bonds are represented by solid black lines and gray
dotted lines, respectively.
|
|
|
|
|
|
The above figures are
reprinted
by permission from Cell Press:
Cell
(2003,
112,
99-0)
copyright 2003.
|
|
|
|
|
|
|
