PDBsum entry: 1ao3

Collagen-binding

PDB-id

1ao3


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Protein chains

Waters ×169

* Residue conservation analysis

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PDB id:

1ao3

Name:

Collagen-binding

Title:

A3 domain of von willebrand factor

Structure:

Von willebrand factor. Chain: a, b. Fragment: a3 domain. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

UniProt:

Chains A, B: P04275 (VWF_HUMAN)

Seq:

Struc:

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Seq:

2813 a.a.

Struc:

187 a.a.

Key:		PfamA domain
		Secondary structure			CATH domain

Resolution:

2.20Å

R-factor:

0.158

R-free:

0.215

Authors:

J.Bienkowski,M.Cruz,R.Handin,R.Liddington

Key ref:

J.Bienkowska et al. (1997). The von willebrand factor A3 domain does not contain a metal ion-dependent adhesion site motif.. J Biol Chem, 272, 25162-25167. [PubMed id: 9312128] [DOI: 10.1074/jbc.272.40.25162]

Date:

16-Jul-97

Release date:

22-Jul-98

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Key reference

DOI no: 10.1074/jbc.272.40.25162 J Biol Chem 272:25162-25167 (1997)

PubMed id: 9312128

The von willebrand factor A3 domain does not contain a metal ion-dependent adhesion site motif.

J.Bienkowska, M.Cruz, A.Atiemo, R.Handin, R.Liddington.

ABSTRACT

von Willebrand factor (vWF) is a multimeric plasma protein that mediates platelet adhesion to exposed subendothelium at sites of vascular injury. The A3 domain of vWF (vWF-A3) forms the principal binding site for collagens type I and III. We report here the crystal structure of the vWF-A3 domain at 2.2-A resolution. As expected, the structure is similar to the integrin I domain but with several novel features. Sequence alignments had suggested that the domain contained an integrin metal ion-dependent adhesion site (MIDAS) motif, but the crystal structure shows that the motif is modified and that no metal ion is bound. We have introduced mutations into the vestigial MIDAS motif and report that, unlike the I domain of integrin alpha2beta1, vWF-A3 continues to bind collagen after disruption of the motif. We conclude that collagen recognition by vWF-A3 occurs by a mechanism different from that of the integrin alpha2beta1.

Selected figure(s)

Figure 3.
Fig. 3. Stereo diagram of the vWF-A3 vestigial MIDAS motif, with schematic main chain and ball-and-stick side chains. The water molecule is labeled W, with hydrogen bonds as dashed red lines. Drawn with MOLSCRIPT (25), RASTER3D (26), and RENDER (27). Figure 4.
Fig. 4. The effect of mutations in the vestigial MIDAS motif on collagen binding. Percentage of normal binding to immobilized^ type I collagen detected by enzyme-linked immunosorbent assay.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (1997, 272, 25162-25167) copyright 1997.

Figures were selected by an automated process.

Literature references that cite this PDB file's key reference

PubMed id Reference

19318682 S.F.De Meyer, H.Deckmyn, and K.Vanhoorelbeke (2009).
von Willebrand factor to the rescue.

Blood, 113, 5049-5057.

19011090 E.Hohenester, T.Sasaki, C.Giudici, R.W.Farndale, and H.P.Bächinger (2008).
Structural basis of sequence-specific collagen recognition by SPARC.

Proc Natl Acad Sci U S A, 105, 18273-18277.

PDB code: 2v53

17389010 C.Martin, L.D.Morales, and M.A.Cruz (2007).
Purified A2 domain of von Willebrand factor binds to the active conformation of von Willebrand factor and blocks the interaction with platelet glycoprotein Ibalpha.

J Thromb Haemost, 5, 1363-1370.

17600523 L.Shapiro, J.Love, and D.R.Colman (2007).
Adhesion molecules in the nervous system: structural insights into function and diversity.

Annu Rev Neurosci, 30, 451-474.

16420575 L.D.Morales, C.Martin, and M.A.Cruz (2006).
The interaction of von Willebrand factor-A1 domain with collagen: mutation G1324S (type 2M von Willebrand disease) impairs the conformational change in A1 domain induced by collagen.

J Thromb Haemost, 4, 417-425.

17098186 T.A.Springer (2006).
Complement and the multifaceted functions of VWA and integrin I domains.

Structure, 14, 1611-1616.

16102037 J.F.Dong (2005).
Cleavage of ultra-large von Willebrand factor by ADAMTS-13 under flow conditions.

J Thromb Haemost, 3, 1710-1716.

12447349 N.Nishida, H.Sumikawa, M.Sakakura, N.Shimba, H.Takahashi, H.Terasawa, E.Suzuki, and I.Shimada (2003).
Collagen-binding mode of vWF-A3 domain determined by a transferred cross-saturation experiment.

Nat Struct Biol, 10, 53-58.

12871266 Z.M.Ruggeri (2003).
Von Willebrand factor, platelets and endothelial cell interactions.

J Thromb Haemost, 1, 1335-1342.

11756664 B.Savage, J.J.Sixma, and Z.M.Ruggeri (2002).
Functional self-association of von Willebrand factor during platelet adhesion under flow.

Proc Natl Acad Sci U S A, 99, 425-430.

12388743 C.A.Whittaker, and R.O.Hynes (2002).
Distribution and evolution of von Willebrand/integrin A domains: widely dispersed domains with roles in cell adhesion and elsewhere.

Mol Biol Cell, 13, 3369-3387.

12102729 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.

11468390 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: 1i8n

10805782 J.R.Huth, E.T.Olejniczak, R.Mendoza, H.Liang, E.A.Harris, M.L.Lupher, A.E.Wilson, S.W.Fesik, and D.E.Staunton (2000).
NMR and mutagenesis evidence for an I domain allosteric site that regulates lymphocyte function-associated antigen 1 ligand binding.

Proc Natl Acad Sci U S A, 97, 5231-5236.

10520599 Z.Li (1999).
The alphaMbeta2 integrin and its role in neutrophil function.

Cell Res, 9, 171-178.

9759493 J.E.Sadler (1998).
Biochemistry and genetics of von Willebrand factor.

Annu Rev Biochem, 67, 395-424.

9501911 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: 1oak

9501084 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.

EMBO J, 17, 1625-1634.

PDB code: 1nub

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.