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Contents |
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* Residue conservation analysis
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DOI no:
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Cell
101:47-56
(2000)
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PubMed id:
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Structural basis of collagen recognition by integrin alpha2beta1.
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J.Emsley,
C.G.Knight,
R.W.Farndale,
M.J.Barnes,
R.C.Liddington.
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ABSTRACT
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We have determined the crystal structure of a complex between the I domain of
integrin alpha2beta1 and a triple helical collagen peptide containing a critical
GFOGER motif. Three loops on the upper surface of the I domain that coordinate a
metal ion also engage the collagen, with a collagen glutamate completing the
coordination sphere of the metal. Comparison with the unliganded I domain
reveals a change in metal coordination linked to a reorganization of the upper
surface that together create a complementary surface for binding collagen.
Conformational changes propagate from the upper surface to the opposite pole of
the domain, suggesting both a basis for affinity regulation and a pathway for
signal transduction. The structural features observed here may represent a
general mechanism for integrin-ligand recognition.
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Selected figure(s)
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Figure 3.
Figure 3. Two Conformations of the Integrin α2-I Domain
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Figure 4.
Figure 4. Comparison of Conformational Changes in the α2-
and αM-I Domains
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The above figures are
reprinted
by permission from Cell Press:
Cell
(2000,
101,
47-56)
copyright 2000.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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Structural basis of host cell recognition by the pilus adhesin from Streptococcus pneumoniae.
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Structure,
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PDB code:
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T.Thijs,
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Structural insights into the interactions between platelet receptors and fibrillar collagen.
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J Biol Chem,
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| |
Structure,
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PDB code:
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F.Carafoli,
N.J.Clout,
and
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(2009).
Crystal structure of the LG1-3 region of the laminin alpha2 chain.
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| |
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284,
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PDB code:
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|
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H.Uysal,
R.Bockermann,
K.S.Nandakumar,
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Structure and pathogenicity of antibodies specific for citrullinated collagen type II in experimental arthritis.
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PDB codes:
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J.A.Fallas,
V.Gauba,
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Solution structure of an ABC collagen heterotrimer reveals a single-register helix stabilized by electrostatic interactions.
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J Biol Chem,
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PDB code:
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J.D.San Antonio,
J.J.Zoeller,
K.Habursky,
K.Turner,
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| |
Biopolymers,
91,
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PDB codes:
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K.Tan,
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FASEB J,
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PDB code:
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M.C.Erat,
D.A.Slatter,
E.D.Lowe,
C.J.Millard,
R.W.Farndale,
I.D.Campbell,
and
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(2009).
Identification and structural analysis of type I collagen sites in complex with fibronectin fragments.
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| |
Proc Natl Acad Sci U S A,
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PDB code:
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|
M.D.Shoulders,
and
R.T.Raines
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Collagen structure and stability.
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(2009).
Small-molecule inhibitors of integrin {alpha}2{beta}1 that prevent pathological thrombus formation via an allosteric mechanism.
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Proc Natl Acad Sci U S A,
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The cytoplasmic domain of anthrax toxin receptor 1 affects binding of the protective antigen.
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Glycoprotein Ib{alpha} inhibitor complex structure reveals a combined steric and allosteric mechanism of von Willebrand factor antagonism.
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| |
Blood,
114,
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PDB code:
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S.H.Lee,
S.Hatakeyama,
S.Y.Yu,
X.Bao,
C.Ohyama,
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and
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(2009).
Core3 O-Glycan Synthase Suppresses Tumor Formation and Metastasis of Prostate Carcinoma PC3 and LNCaP Cells through Down-regulation of {alpha}2{beta}1 Integrin Complex.
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J Biol Chem,
284,
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Identification of a VWF peptide antagonist that blocks platelet adhesion under high shear conditions by selectively inhibiting the VWF-collagen interaction.
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The crystal structure of cobra venom factor, a cofactor for C3- and C5-convertase CVFBb.
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Structure,
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Y.Xu,
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and
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PDB code:
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Y.C.Yeh,
C.Z.Wang,
and
M.J.Tang
(2009).
Discoidin domain receptor 1 activation suppresses alpha2beta1 integrin-dependent cell spreading through inhibition of Cdc42 activity.
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J Cell Physiol,
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Y.Sugita,
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| |
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E.Hohenester,
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(2008).
Structural basis of sequence-specific collagen recognition by SPARC.
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| |
Proc Natl Acad Sci U S A,
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|
PDB code:
|
|
|
|
|
|
|
|
H.Ido,
S.Ito,
Y.Taniguchi,
M.Hayashi,
R.Sato-Nishiuchi,
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J Biol Chem,
283,
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H.Zhang,
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An unusual allosteric mobility of the C-terminal helix of a high-affinity alphaL integrin I domain variant bound to ICAM-5.
|
| |
Mol Cell,
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PDB code:
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I.C.Munnix,
K.Gilio,
P.R.Siljander,
N.Raynal,
M.A.Feijge,
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H.Deckmyn,
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R.W.Farndale,
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J.W.Heemskerk
(2008).
Collagen-mimetic peptides mediate flow-dependent thrombus formation by high- or low-affinity binding of integrin alpha2beta1 and glycoprotein VI.
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| |
J Thromb Haemost,
6,
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J.M.Cosemans,
B.F.Iserbyt,
H.Deckmyn,
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J.W.Heemskerk
(2008).
Multiple ways to switch platelet integrins on and off.
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J Thromb Haemost,
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L.J.Lambert,
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J.W.Smith,
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F.M.Marassi
(2008).
Competitive interactions of collagen and a jararhagin-derived disintegrin peptide with the integrin alpha2-I domain.
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J Biol Chem,
283,
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L.R.Fiedler,
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D.G.Seidler,
D.Aeschlimann,
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J.A.Eble
(2008).
Decorin regulates endothelial cell motility on collagen I through activation of insulin-like growth factor I receptor and modulation of alpha2beta1 integrin activity.
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J Biol Chem,
283,
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N.S.Seo,
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M.Höök,
and
M.K.Estes
(2008).
Inaugural article: integrins alpha1beta1 and alpha2beta1 are receptors for the rotavirus enterotoxin.
|
| |
Proc Natl Acad Sci U S A,
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O.Inoue,
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Science,
297,
1176-1179.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
G.A.Di Lullo,
S.M.Sweeney,
J.Korkko,
L.Ala-Kokko,
and
J.D.San Antonio
(2002).
Mapping the ligand-binding sites and disease-associated mutations on the most abundant protein in the human, type I collagen.
|
| |
J Biol Chem,
277,
4223-4231.
|
|
|
|
|
|
|
G.B.Legge,
G.M.Morris,
M.F.Sanner,
Y.Takada,
A.J.Olson,
and
F.Grynszpan
(2002).
Model of the alphaLbeta2 integrin I-domain/ICAM-1 DI interface suggests that subtle changes in loop orientation determine ligand specificity.
|
| |
Proteins,
48,
151-160.
|
|
|
PDB code:
|
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|
|
|
|
|
G.E.Jarvis,
B.T.Atkinson,
D.C.Snell,
and
S.P.Watson
(2002).
Distinct roles of GPVI and integrin alpha(2)beta(1) in platelet shape change and aggregation induced by different collagens.
|
| |
Br J Pharmacol,
137,
107-117.
|
|
|
|
|
|
|
J.E.Garbarino,
and
I.R.Gibbons
(2002).
Expression and genomic analysis of midasin, a novel and highly conserved AAA protein distantly related to dynein.
|
| |
BMC Genomics,
3,
18.
|
|
|
|
|
|
|
J.H.Min,
H.Yang,
M.Ivan,
F.Gertler,
W.G.Kaelin,
and
N.P.Pavletich
(2002).
Structure of an HIF-1alpha -pVHL complex: hydroxyproline recognition in signaling.
|
| |
Science,
296,
1886-1889.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
J.L.Alonso,
M.Essafi,
J.P.Xiong,
T.Stehle,
and
M.A.Arnaout
(2002).
Does the integrin alphaA domain act as a ligand for its betaA domain?
|
| |
Curr Biol,
12,
R340-R342.
|
|
|
|
|
|
|
J.Takagi,
and
T.A.Springer
(2002).
Integrin activation and structural rearrangement.
|
| |
Immunol Rev,
186,
141-163.
|
|
|
|
|
|
|
J.W.Smith,
H.Le Calvez,
L.Parra-Gessert,
N.E.Preece,
X.Jia,
and
N.Assa-Munt
(2002).
Selection and structure of ion-selective ligands for platelet integrin alpha IIb(beta) 3.
|
| |
J Biol Chem,
277,
10298-10305.
|
|
|
PDB codes:
|
|
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|
|
|
|
|
K.E.Gottschalk,
P.D.Adams,
A.T.Brunger,
and
H.Kessler
(2002).
Transmembrane signal transduction of the alpha(IIb)beta(3) integrin.
|
| |
Protein Sci,
11,
1800-1812.
|
|
|
|
|
|
|
K.Fukuda,
T.A.Doggett,
L.A.Bankston,
M.A.Cruz,
T.G.Diacovo,
and
R.C.Liddington
(2002).
Structural basis of von Willebrand factor activation by the snake toxin botrocetin.
|
| |
Structure,
10,
943-950.
|
|
|
PDB codes:
|
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|
K.Matuschewski,
A.C.Nunes,
V.Nussenzweig,
and
R.Ménard
(2002).
Plasmodium sporozoite invasion into insect and mammalian cells is directed by the same dual binding system.
|
| |
EMBO J,
21,
1597-1606.
|
|
|
|
|
|
|
K.Welzenbach,
U.Hommel,
and
G.Weitz-Schmidt
(2002).
Small molecule inhibitors induce conformational changes in the I domain and the I-like domain of lymphocyte function-associated antigen-1. Molecular insights into integrin inhibition.
|
| |
J Biol Chem,
277,
10590-10598.
|
|
|
|
|
|
|
L.S.Mizoue,
and
W.J.Chazin
(2002).
Engineering and design of ligand-induced conformational change in proteins.
|
| |
Curr Opin Struct Biol,
12,
459-463.
|
|
|
|
|
|
|
M.A.Arnaout
(2002).
Integrin structure: new twists and turns in dynamic cell adhesion.
|
| |
Immunol Rev,
186,
125-140.
|
|
|
|
|
|
|
M.A.Arnaout,
S.L.Goodman,
and
J.P.Xiong
(2002).
Coming to grips with integrin binding to ligands.
|
| |
Curr Opin Cell Biol,
14,
641-651.
|
|
|
|
|
|
|
M.Shimaoka,
C.Lu,
A.Salas,
T.Xiao,
J.Takagi,
and
T.A.Springer
(2002).
Stabilizing the integrin alpha M inserted domain in alternative conformations with a range of engineered disulfide bonds.
|
| |
Proc Natl Acad Sci U S A,
99,
16737-16741.
|
|
|
|
|
|
|
M.Shimaoka,
J.Takagi,
and
T.A.Springer
(2002).
Conformational regulation of integrin structure and function.
|
| |
Annu Rev Biophys Biomol Struct,
31,
485-516.
|
|
|
|
|
|
|
N.Beglova,
S.C.Blacklow,
J.Takagi,
and
T.A.Springer
(2002).
Cysteine-rich module structure reveals a fulcrum for integrin rearrangement upon activation.
|
| |
Nat Struct Biol,
9,
282-287.
|
|
|
PDB code:
|
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|
|
|
|
|
|
N.Hogg,
R.Henderson,
B.Leitinger,
A.McDowall,
J.Porter,
and
P.Stanley
(2002).
Mechanisms contributing to the activity of integrins on leukocytes.
|
| |
Immunol Rev,
186,
164-171.
|
|
|
|
|
|
|
O.Holtkötter,
B.Nieswandt,
N.Smyth,
W.Müller,
M.Hafner,
V.Schulte,
T.Krieg,
and
B.Eckes
(2002).
Integrin alpha 2-deficient mice develop normally, are fertile, but display partially defective platelet interaction with collagen.
|
| |
J Biol Chem,
277,
10789-10794.
|
|
|
|
|
|
|
P.Gresele,
and
G.Agnelli
(2002).
Novel approaches to the treatment of thrombosis.
|
| |
Trends Pharmacol Sci,
23,
25-32.
|
|
|
|
|
|
|
Q.Ma,
M.Shimaoka,
C.Lu,
H.Jing,
C.V.Carman,
and
T.A.Springer
(2002).
Activation-induced conformational changes in the I domain region of lymphocyte function-associated antigen 1.
|
| |
J Biol Chem,
277,
10638-10641.
|
|
|
|
|
|
|
R.C.Liddington,
and
M.H.Ginsberg
(2002).
Integrin activation takes shape.
|
| |
J Cell Biol,
158,
833-839.
|
|
|
|
|
|
|
Y.M.Xiong,
T.A.Haas,
and
L.Zhang
(2002).
Identification of functional segments within the beta2I-domain of integrin alphaMbeta2.
|
| |
J Biol Chem,
277,
46639-46644.
|
|
|
|
|
|
|
C.A.Curat,
M.Eck,
X.Dervillez,
and
W.F.Vogel
(2001).
Mapping of epitopes in discoidin domain receptor 1 critical for collagen binding.
|
| |
J Biol Chem,
276,
45952-45958.
|
|
|
|
|
|
|
C.Lu,
M.Shimaoka,
M.Ferzly,
C.Oxvig,
J.Takagi,
and
T.A.Springer
(2001).
An isolated, surface-expressed I domain of the integrin alphaLbeta2 is sufficient for strong adhesive function when locked in the open conformation with a disulfide bond.
|
| |
Proc Natl Acad Sci U S A,
98,
2387-2392.
|
|
|
|
|
|
|
C.Lu,
M.Shimaoka,
Q.Zang,
J.Takagi,
and
T.A.Springer
(2001).
Locking in alternate conformations of the integrin alphaLbeta2 I domain with disulfide bonds reveals functional relationships among integrin domains.
|
| |
Proc Natl Acad Sci U S A,
98,
2393-2398.
|
|
|
|
|
|
|
E.G.Huizinga,
A.Schouten,
T.M.Connolly,
J.Kroon,
J.J.Sixma,
and
P.Gros
(2001).
The structure of leech anti-platelet protein, an inhibitor of haemostasis.
|
| |
Acta Crystallogr D Biol Crystallogr,
57,
1071-1078.
|
|
|
PDB code:
|
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|
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|
|
|
J.P.Evans
(2001).
Fertilin beta and other ADAMs as integrin ligands: insights into cell adhesion and fertilization.
|
| |
Bioessays,
23,
628-639.
|
|
|
|
|
|
|
J.P.Xiong,
T.Stehle,
B.Diefenbach,
R.Zhang,
R.Dunker,
D.L.Scott,
A.Joachimiak,
S.L.Goodman,
and
M.A.Arnaout
(2001).
Crystal structure of the extracellular segment of integrin alpha Vbeta3.
|
| |
Science,
294,
339-345.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
M.J.Humphries,
and
A.P.Mould
(2001).
Structure. An anthropomorphic integrin.
|
| |
Science,
294,
316-317.
|
|
|
|
|
|
|
M.Shimaoka,
C.Lu,
R.T.Palframan,
U.H.von Andrian,
A.McCormack,
J.Takagi,
and
T.A.Springer
(2001).
Reversibly locking a protein fold in an active conformation with a disulfide bond: integrin alphaL I domains with high affinity and antagonist activity in vivo.
|
| |
Proc Natl Acad Sci U S A,
98,
6009-6014.
|
|
|
|
|
|
|
R.R.Hantgan,
M.Rocco,
C.Nagaswami,
and
J.W.Weisel
(2001).
Binding of a fibrinogen mimetic stabilizes integrin alphaIIbbeta3's open conformation.
|
| |
Protein Sci,
10,
1614-1626.
|
|
|
|
|
|
|
A.V.Persikov,
J.A.Ramshaw,
and
B.Brodsky
(2000).
Collagen model peptides: Sequence dependence of triple-helix stability.
|
| |
Biopolymers,
55,
436-450.
|
|
|
|
|
|
|
J.Bella,
and
H.M.Berman
(2000).
Integrin-collagen complex: a metal-glutamate handshake.
|
| |
Structure,
8,
R121-R126.
|
|
|
|
|
|
|
N.Armstrong,
and
E.Gouaux
(2000).
Mechanisms for activation and antagonism of an AMPA-sensitive glutamate receptor: crystal structures of the GluR2 ligand binding core.
|
| |
Neuron,
28,
165-181.
|
|
|
PDB codes:
|
|
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|
|
W.W.Agace,
J.M.Higgins,
B.Sadasivan,
M.B.Brenner,
and
C.M.Parker
(2000).
T-lymphocyte-epithelial-cell interactions: integrin alpha(E)(CD103)beta(7), LEEP-CAM and chemokines.
|
| |
Curr Opin Cell Biol,
12,
563-568.
|
|
|
|
|
|
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
code is
shown on the right.
|
 |
Links
