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* Residue conservation analysis
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DOI no:
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J Biol Chem
272:28512-28517
(1997)
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PubMed id:
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Crystal structure of the I domain from integrin alpha2beta1.
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J.Emsley,
S.L.King,
J.M.Bergelson,
R.C.Liddington.
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ABSTRACT
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We have determined the high resolution crystal structure of the I domain from
the alpha-subunit of the integrin alpha2beta1, a cell surface adhesion receptor
for collagen and the human pathogen echovirus-1. The domain, as expected, adopts
the dinucleotide-binding fold, and contains a metal ion-dependent adhesion site
motif with bound Mg2+ at the top of the beta-sheet. Comparison with the crystal
structures of the leukocyte integrin I domains reveals a new helix (the C-helix)
protruding from the metal ion-dependent adhesion site face of the domain which
creates a groove centered on the magnesium ion. Modeling of a collagen triple
helix into the groove suggests that a glutamic acid side chain from collagen can
coordinate the metal ion, and that the C-helix insert is a major determinant of
binding specificity. The binding site for echovirus-1 maps to a distinct surface
of the alpha2-I domain (one edge of the beta-sheet), consistent with data
showing that virus and collagen binding occur by different mechanisms.
Comparison with the homologous von Willebrand factor A3 domain, which also binds
collagen, suggests that the two domains bind collagen in different ways.
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Selected figure(s)
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Figure 3.
Fig. 3. Close up view of the  2-I domain
MIDAS motif. Loops are shown schematically in gray, together
with the side chains^ of the MIDAS motif, the Mg^2+ ion (M), and
three coordinating water molecules (  ).
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Figure 4.
Fig. 4. The MIDAS face of the integrin I domains ( 2-I, M-I, and
L-I) and
vWF-A3. The view is perpendicular to that in Figs.^ 1 and 3.
Helices are shown as thick tubes,  -strands and
loops^ as thin tubes. The side chains of the MIDAS motif are
shown, with^ the metal ions as crosses.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(1997,
272,
28512-28517)
copyright 1997.
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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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PDB code:
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PDB codes:
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L.Galois,
S.Hutasse,
D.Cortial,
C.F.Rousseau,
L.Grossin,
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PDB code:
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M.Jin,
I.Andricioaei,
and
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Conversion between three conformational states of integrin I domains with a C-terminal pull spring studied with molecular dynamics.
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Structure, 12,
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R.W.Farndale,
J.J.Sixma,
M.J.Barnes,
and
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J Thromb Haemost, 2,
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J.J.Wilson,
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A.Okabe,
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(2003).
A bacterial collagen-binding domain with novel calcium-binding motif controls domain orientation.
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EMBO J, 22,
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PDB codes:
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K.Horii,
D.Okuda,
T.Morita,
and
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(2003).
Structural characterization of EMS16, an antagonist of collagen receptor (GPIa/IIa) from the venom of Echis multisquamatus.
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Biochemistry, 42,
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PDB code:
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M.Shimaoka,
T.Xiao,
J.H.Liu,
Y.Yang,
Y.Dong,
C.D.Jun,
A.McCormack,
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A.Joachimiak,
J.Takagi,
J.H.Wang,
and
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Structures of the alpha L I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation.
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Cell, 112,
99.
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PDB codes:
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T.Vorup-Jensen,
C.Ostermeier,
M.Shimaoka,
U.Hommel,
and
T.A.Springer
(2003).
Structure and allosteric regulation of the alpha X beta 2 integrin I domain.
|
| |
Proc Natl Acad Sci U S A, 100,
1873-1878.
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PDB code:
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A.Aquilina,
M.Korda,
J.M.Bergelson,
M.J.Humphries,
R.W.Farndale,
and
D.Tuckwell
(2002).
A novel gain-of-function mutation of the integrin alpha2 VWFA domain.
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Eur J Biochem, 269,
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C.A.Whittaker,
and
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(2002).
Distribution and evolution of von Willebrand/integrin A domains: widely dispersed domains with roles in cell adhesion and elsewhere.
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Mol Biol Cell, 13,
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D.E.Gullberg,
and
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Collagen-binding I domain integrins--what do they do?
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Prog Histochem Cytochem, 37,
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J.Takagi,
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Integrin activation and structural rearrangement.
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Immunol Rev, 186,
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(2002).
Plasmodium sporozoite invasion into insect and mammalian cells is directed by the same dual binding system.
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Engineering and design of ligand-induced conformational change in proteins.
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Curr Opin Struct Biol, 12,
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M.A.Arnaout
(2002).
Integrin structure: new twists and turns in dynamic cell adhesion.
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Immunol Rev, 186,
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J.Takagi,
and
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Conformational regulation of integrin structure and function.
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Annu Rev Biophys Biomol Struct, 31,
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D.S.Maxwell,
T.P.Kogan,
Q.Chen,
J.Li,
J.Kassir,
G.W.Holland,
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(2002).
A 3D structure model of integrin alpha 4 beta 1 complex: I. Construction of a homology model of beta 1 and ligand binding analysis.
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Biophys J, 82,
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E.G.Huizinga,
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T.M.Connolly,
J.Kroon,
J.J.Sixma,
and
P.Gros
(2001).
The structure of leech anti-platelet protein, an inhibitor of haemostasis.
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| |
Acta Crystallogr D Biol Crystallogr, 57,
1071-1078.
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PDB code:
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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.
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| |
Proc Natl Acad Sci U S A, 98,
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R.H.Hyland,
W.A.Douglass,
S.M.Tan,
and
S.K.Law
(2001).
Chimeras of the integrin beta subunit mid-region reveal regions required for heterodimer formation and for activation.
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| |
Cell Commun Adhes, 8,
61-69.
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C.C.Deivanayagam,
R.L.Rich,
M.Carson,
R.T.Owens,
S.Danthuluri,
T.Bice,
M.Höök,
and
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(2000).
Novel fold and assembly of the repetitive B region of the Staphylococcus aureus collagen-binding surface protein.
|
| |
Structure, 8,
67-78.
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PDB codes:
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C.Marcinkiewicz,
R.R.Lobb,
M.M.Marcinkiewicz,
J.L.Daniel,
J.B.Smith,
C.Dangelmaier,
P.H.Weinreb,
D.A.Beacham,
and
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(2000).
Isolation and characterization of EMS16, a C-lectin type protein from Echis multisquamatus venom, a potent and selective inhibitor of the alpha2beta1 integrin.
|
| |
Biochemistry, 39,
9859-9867.
|
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G.Bitan,
L.Scheibler,
D.F.Mierke,
M.Rosenblatt,
and
M.Chorev
(2000).
Ligand-integrin alpha v beta 3 interaction determined by photoaffinity cross-linking: a challenge to the prevailing model.
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| |
Biochemistry, 39,
11014-11023.
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J.Bella,
and
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(2000).
Integrin-collagen complex: a metal-glutamate handshake.
|
| |
Structure, 8,
R121-R126.
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|
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J.R.Huth,
E.T.Olejniczak,
R.Mendoza,
H.Liang,
E.A.Harris,
M.L.Lupher,
A.E.Wilson,
S.W.Fesik,
and
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(2000).
NMR and mutagenesis evidence for an I domain allosteric site that regulates lymphocyte function-associated antigen 1 ligand binding.
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| |
Proc Natl Acad Sci U S A, 97,
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K.S.Taraszka,
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D.A.Mandelbrot,
J.H.Wang,
and
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(2000).
Molecular basis for leukocyte integrin alpha(E)beta(7) adhesion to epithelial (E)-cadherin.
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| |
J Exp Med, 191,
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C.Oxvig,
C.Lu,
and
T.A.Springer
(1999).
Conformational changes in tertiary structure near the ligand binding site of an integrin I domain.
|
| |
Proc Natl Acad Sci U S A, 96,
2215-2220.
|
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|
C.Y.Chiu,
P.Mathias,
G.R.Nemerow,
and
P.L.Stewart
(1999).
Structure of adenovirus complexed with its internalization receptor, alphavbeta5 integrin.
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| |
J Virol, 73,
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|
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H.A.Gardner
(1999).
Integrin signaling in fibrosis and scleroderma.
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| |
Curr Rheumatol Rep, 1,
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P.J.Gotwals,
G.Chi-Rosso,
S.T.Ryan,
I.Sizing,
M.Zafari,
C.Benjamin,
J.Singh,
S.Y.Venyaminov,
R.B.Pepinsky,
and
V.Koteliansky
(1999).
Divalent cations stabilize the alpha 1 beta 1 integrin I domain.
|
| |
Biochemistry, 38,
8280-8288.
|
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|
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T.A.Salminen,
Y.Nymalm,
J.Kankare,
J.Käpylä,
J.Heino,
and
M.S.Johnson
(1999).
Production, crystallization and preliminary X-ray analysis of the human integrin alpha1 I domain.
|
| |
Acta Crystallogr D Biol Crystallogr, 55,
1365-1367.
|
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|
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|
|
Z.Li
(1999).
The alphaMbeta2 integrin and its role in neutrophil function.
|
| |
Cell Res, 9,
171-178.
|
|
|
|
|
|
|
A.Al-Shamkhani,
and
S.K.Law
(1998).
Expression of the H52 epitope on the beta2 subunit is dependent on its interaction with the alpha subunits of the leukocyte integrins LFA-1, Mac-1 and p150,95 and the presence of Ca2+.
|
| |
Eur J Immunol, 28,
3291-3300.
|
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|
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|
|
E.T.Baldwin,
R.W.Sarver,
G.L.Bryant,
K.A.Curry,
M.B.Fairbanks,
B.C.Finzel,
R.L.Garlick,
R.L.Heinrikson,
N.C.Horton,
L.L.Kelley,
A.M.Mildner,
J.B.Moon,
J.E.Mott,
V.T.Mutchler,
C.S.Tomich,
K.D.Watenpaugh,
and
V.H.Wiley
(1998).
Cation binding to the integrin CD11b I domain and activation model assessment.
|
| |
Structure, 6,
923-935.
|
|
|
PDB codes:
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|
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R.Celikel,
K.I.Varughese,
Madhusudan,
A.Yoshioka,
J.Ware,
Z.M.Ruggeri,
R.Celikel,
K.I.Varughese,
Madhusudan,
A.Yoshioka,
J.Ware,
and
Z.M.Ruggeri
(1998).
Crystal structure of the von Willebrand factor A1 domain in complex with the function blocking NMC-4 Fab.
|
| |
Nat Struct Biol, 5,
189-194.
|
|
|
PDB code:
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R.L.Rich,
B.Demeler,
K.Ashby,
C.C.Deivanayagam,
J.W.Petrich,
J.M.Patti,
S.V.Narayana,
and
M.Höök
(1998).
Domain structure of the Staphylococcus aureus collagen adhesin.
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| |
Biochemistry, 37,
15423-15433.
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R.Li,
P.Rieu,
D.L.Griffith,
D.Scott,
and
M.A.Arnaout
(1998).
Two functional states of the CD11b A-domain: correlations with key features of two Mn2+-complexed crystal structures.
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| |
J Cell Biol, 143,
1523-1534.
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R.Liddington,
and
L.Bankston
(1998).
The integrin I domain: crystals, metals and related artefacts.
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| |
Structure, 6,
937-938.
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S.K.Dickeson,
M.Bhattacharyya-Pakrasi,
N.L.Mathis,
P.H.Schlesinger,
and
S.A.Santoro
(1998).
Ligand binding results in divalent cation displacement from the alpha 2 beta 1 integrin I domain: evidence from terbium luminescence spectroscopy.
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| |
Biochemistry, 37,
11280-11288.
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T.Sasaki,
E.Hohenester,
W.Göhring,
and
R.Timpl
(1998).
Crystal structure and mapping by site-directed mutagenesis of the collagen-binding epitope of an activated form of BM-40/SPARC/osteonectin.
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| |
EMBO J, 17,
1625-1634.
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PDB code:
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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.
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Links
