 |
PDBsum entry 1n9z
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Cell adhesion
|
PDB id
|
|
|
|
1n9z
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
|
Biochem J
372:121-127
(2003)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Engineered allosteric mutants of the integrin alphaMbeta2 I domain: structural and functional studies.
|
|
C.J.McCleverty,
R.C.Liddington.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
The alpha-I domain, found in the alpha-subunit of the leucocyte integrins such
as alphaMbeta2 and alphaLbeta2, switches between the open and closed tertiary
conformations, reflecting the high- and low-affinity ligand-binding states of
the integrin that are required for regulated cell adhesion and migration. In the
present study we show, by using point mutations and engineered disulphide bonds,
that ligand affinity can be reduced or increased allosterically by altering the
equilibrium between the closed and open states. We determined equilibrium
constants for the binding of two ligands, fibrinogen and intercellular
cell-adhesion molecule 1, to the alphaM-I domain by surface plasmon resonance,
and determined crystal structures of a low-affinity mutant. Locking the domain
in the open conformation increases affinity by a factor of no greater than 10,
consistent with a closely balanced equilibrium between the two conformations in
the absence of ligand. This behaviour contrasts with that of the unliganded
alphaL-I domain, for which the equilibrium lies strongly in favour of the closed
conformation. These results suggest significant differences in the way the
parent integrins regulate I domain conformation and hence ligand affinity.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
S.E.Jenkinson,
S.A.Whawell,
B.M.Swales,
E.M.Corps,
P.J.Kilshaw,
and
P.M.Farthing
(2011).
The αE(CD103)β7 integrin interacts with oral and skin keratinocytes in an E-cadherin-independent manner*.
|
| |
Immunology,
132,
188-196.
|
|
|
|
|
|
|
X.Hu,
S.Kang,
C.Lefort,
M.Kim,
and
M.M.Jin
(2010).
Combinatorial libraries against libraries for selecting neoepitope activation-specific antibodies.
|
| |
Proc Natl Acad Sci U S A,
107,
6252-6257.
|
|
|
|
|
|
|
B.H.Luo,
J.Karanicolas,
L.D.Harmacek,
D.Baker,
and
T.A.Springer
(2009).
Rationally Designed Integrin {beta}3 Mutants Stabilized in the High Affinity Conformation.
|
| |
J Biol Chem,
284,
3917-3924.
|
|
|
|
|
|
|
M.H.Faridi,
D.Maiguel,
C.J.Barth,
D.Stoub,
R.Day,
S.Schürer,
and
V.Gupta
(2009).
Identification of novel agonists of the integrin CD11b/CD18.
|
| |
Bioorg Med Chem Lett,
19,
6902-6906.
|
|
|
|
|
|
|
A.Pathak,
V.S.Deshpande,
R.M.McMeeking,
and
A.G.Evans
(2008).
The simulation of stress fibre and focal adhesion development in cells on patterned substrates.
|
| |
J R Soc Interface,
5,
507-524.
|
|
|
|
|
|
|
S.K.Nath,
S.Han,
X.Kim-Howard,
J.A.Kelly,
P.Viswanathan,
G.S.Gilkeson,
W.Chen,
C.Zhu,
R.P.McEver,
R.P.Kimberly,
M.E.Alarcón-Riquelme,
T.J.Vyse,
Q.Z.Li,
E.K.Wakeland,
J.T.Merrill,
J.A.James,
K.M.Kaufman,
J.M.Guthridge,
and
J.B.Harley
(2008).
A nonsynonymous functional variant in integrin-alpha(M) (encoded by ITGAM) is associated with systemic lupus erythematosus.
|
| |
Nat Genet,
40,
152-154.
|
|
|
|
|
|
|
V.Krishnan,
Y.Xu,
K.Macon,
J.E.Volanakis,
and
S.V.Narayana
(2007).
The crystal structure of C2a, the catalytic fragment of classical pathway C3 and C5 convertase of human complement.
|
| |
J Mol Biol,
367,
224-233.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
M.Jin,
G.Song,
C.V.Carman,
Y.S.Kim,
N.S.Astrof,
M.Shimaoka,
D.K.Wittrup,
and
T.A.Springer
(2006).
Directed evolution to probe protein allostery and integrin I domains of 200,000-fold higher affinity.
|
| |
Proc Natl Acad Sci U S A,
103,
5758-5763.
|
|
|
|
|
|
|
D.Ehirchiou,
Y.M.Xiong,
Y.Li,
S.Brew,
and
L.Zhang
(2005).
Dual function for a unique site within the beta2I domain of integrin alphaMbeta2.
|
| |
J Biol Chem,
280,
8324-8331.
|
|
|
|
|
|
|
M.A.Arnaout,
B.Mahalingam,
and
J.P.Xiong
(2005).
Integrin structure, allostery, and bidirectional signaling.
|
| |
Annu Rev Cell Dev Biol,
21,
381-410.
|
|
|
|
|
|
|
R.L.Rich,
and
D.G.Myszka
(2005).
Survey of the year 2003 commercial optical biosensor literature.
|
| |
J Mol Recognit,
18,
1.
|
|
|
|
|
|
|
A.A.Bhattacharya,
M.L.Lupher,
D.E.Staunton,
and
R.C.Liddington
(2004).
Crystal structure of the A domain from complement factor B reveals an integrin-like open conformation.
|
| |
Structure,
12,
371-378.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
A.P.Mould,
and
M.J.Humphries
(2004).
Regulation of integrin function through conformational complexity: not simply a knee-jerk reaction?
|
| |
Curr Opin Cell Biol,
16,
544-551.
|
|
|
|
|
|
|
D.B.Lacy,
D.J.Wigelsworth,
H.M.Scobie,
J.A.Young,
and
R.J.Collier
(2004).
Crystal structure of the von Willebrand factor A domain of human capillary morphogenesis protein 2: an anthrax toxin receptor.
|
| |
Proc Natl Acad Sci U S A,
101,
6367-6372.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
D.J.Wigelsworth,
B.A.Krantz,
K.A.Christensen,
D.B.Lacy,
S.J.Juris,
and
R.J.Collier
(2004).
Binding stoichiometry and kinetics of the interaction of a human anthrax toxin receptor, CMG2, with protective antigen.
|
| |
J Biol Chem,
279,
23349-23356.
|
|
|
|
|
|
The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
|
|
Links
