PDBsum entry: 1vca

Cell adhesion protein

PDB-id

1vca


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PDB id:

1vca

Name:

Cell adhesion protein

Title:

Crystal structure of an integrin-binding fragment of vascular cell adhesion molecule-1 at 1.8 angstroms resolution

Structure:

Human vascular cell adhesion molecule-1. Chain: a, b. Synonym: vcam-d1,2. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Strain: hw1110. Expressed in: escherichia coli. Expression_system_taxid: 562

UniProt:

Chains A, B: P19320 (VCAM1_HUMAN)

Seq:

Struc:

Seq:

Struc:

Seq:

739 a.a.

Struc:

199 a.a.

Key:		PfamA domain
		Secondary structure			CATH domain

Resolution:

1.80Å

R-factor:

0.202

Authors:

E.Y.Jones,K.Harlos,M.J.Bottomley,R.C.Robinson,P.C.Driscoll, R.M.Edwards,J.M.Clements,T.J.Dudgeon,D.I.Stuart

Key ref:

E.Y.Jones et al. (1995). Crystal structure of an integrin-binding fragment of vascular cell adhesion molecule-1 at 1.8 A resolution.. Nature, 373, 539-544. [PubMed id: 7531291] [DOI: 10.1038/373539a0]

Date:

21-Mar-95

Release date:

15-Sep-95

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Key reference

DOI no: 10.1038/373539a0 Nature 373:539-544 (1995)

PubMed id: 7531291

Crystal structure of an integrin-binding fragment of vascular cell adhesion molecule-1 at 1.8 A resolution.

E.Y.Jones, K.Harlos, M.J.Bottomley, R.C.Robinson, P.C.Driscoll, R.M.Edwards, J.M.Clements, T.J.Dudgeon, D.I.Stuart.

ABSTRACT

The cell-surface glycoprotein vascular cell adhesion molecule-1 (VCAM-1; ref. 1) mediates intercellular adhesion by specific binding to the integrin very-late antigen-4 (VLA-4, alpha 4 beta 1; ref. 3). VCAM-1, with the intercellular adhesion molecules ICAM-1, ICAM-2, ICAM-3 and the mucosal vascular addressin MAd-CAM-1, forms an integrin-binding subgroup of the immunoglobulin superfamily. In addition to their clinical relevance in inflammation, these molecules act as cellular receptors for viral and parasitic agents. The predominant form of VCAM-1 in vivo has an amino-terminal extracellular region comprising seven immunoglobulin-like domains. Functional studies have identified a conserved integrin-binding motif in domains 1 and 4, variants of which are present in the N-terminal domain of all members of the immunoglobulin superfamily subgroup. We report here the crystal structure of a VLA-4-binding fragment composed of the first two domains of VCAM-1. The integrin-binding motif (Q38IDSPL) is highly exposed and forms the N-terminal region of the loop between beta-strands C and D of domain 1. This motif exhibits a distinctive conformation which we predict will be common to all the integrin-binding IgSF molecules. These, and additional data, map VLA-4 binding to the face of the CFG beta-sheet, the surface previously identified as the site for intercellular adhesive interactions between members of the immunoglobulin superfamily.

Literature references that cite this PDB file's key reference

PubMed id Reference

18430721 X.L.Yu, T.Hu, J.M.Du, J.P.Ding, X.M.Yang, J.Zhang, B.Yang, X.Shen, Z.Zhang, W.D.Zhong, N.Wen, H.Jiang, P.Zhu, and Z.N.Chen (2008).
Crystal structure of HAb18G/CD147: implications for immunoglobulin superfamily homophilic adhesion.

J Biol Chem, 283, 18056-18065.

PDB code: 3b5h

15827972 A.Zubia, L.Mendoza, S.Vivanco, E.Aldaba, T.Carrascal, B.Lecea, A.Arrieta, T.Zimmerman, F.Vidal-Vanaclocha, and F.P.Cossío (2005).
Application of Stereocontrolled Stepwise [3+2] Cycloadditions to the Preparation of Inhibitors of alpha(4)beta(1)-Integrin-Mediated Hepatic Melanoma Metastasis.

Angew Chem Int Ed Engl, 44, 2903-2907.

15778960 M.Król, I.Roterman, B.Piekarska, L.Konieczny, J.Rybarska, B.Stopa, and P.Spólnik (2005).
Analysis of correlated domain motions in IgG light chain reveals possible mechanisms of immunological signal transduction.

Proteins, 59, 545-554.

14871459 H.J.Huttunen, and H.Rauvala (2004).
Amphoterin as an extracellular regulator of cell motility: from discovery to disease.

J Intern Med, 255, 351-366.

11807247 J.Dando, K.W.Wilkinson, S.Ortlepp, D.J.King, and R.L.Brady (2002).
A reassessment of the MAdCAM-1 structure and its role in integrin recognition.

Acta Crystallogr D Biol Crystallogr, 58, 233-241.

PDB code: 1gsm

11980922 Z.Li, M.J.Calzada, J.M.Sipes, J.A.Cashel, H.C.Krutzsch, D.S.Annis, D.F.Mosher, and D.D.Roberts (2002).
Interactions of thrombospondins with alpha4beta1 integrin and CD47 differentially modulate T cell behavior.

J Cell Biol, 157, 509-519.

11574465 M.Kvansakul, M.Hopf, A.Ries, R.Timpl, and E.Hohenester (2001).
Structural basis for the high-affinity interaction of nidogen-1 with immunoglobulin-like domain 3 of perlecan.

EMBO J, 20, 5342-5346.

PDB code: 1gl4

11679722 P.Taylor, M.Bilsland, and M.D.Walkinshaw (2001).
A new conformation of the integrin-binding fragment of human VCAM-1 crystallizes in a highly hydrated packing arrangement.

Acta Crystallogr D Biol Crystallogr, 57, 1579-1583.

PDB code: 1ij9

10618369 D.J.Stauber, A.D.DiGabriele, and W.A.Hendrickson (2000).
Structural interactions of fibroblast growth factor receptor with its ligands.

Proc Natl Acad Sci U S A, 97, 49-54.

PDB code: 1djs

10933504 I.Callebaut, D.Gilgès, I.Vigon, and J.P.Mornon (2000).
HYR, an extracellular module involved in cellular adhesion and related to the immunoglobulin-like fold.

Protein Sci, 9, 1382-1390.

10790430 K.S.Taraszka, J.M.Higgins, K.Tan, D.A.Mandelbrot, J.H.Wang, and M.B.Brenner (2000).
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J Exp Med, 191, 1555-1567.

10861932 M.A.Bowen, A.A.Aruffo, and J.Bajorath (2000).
Cell surface receptors and their ligands: in vitro analysis of CD6-CD166 interactions.

Proteins, 40, 420-428.

10880433 X.Jiang, O.Gurel, E.A.Mendiaz, G.W.Stearns, C.L.Clogston, H.S.Lu, T.D.Osslund, R.S.Syed, K.E.Langley, and W.A.Hendrickson (2000).
Structure of the active core of human stem cell factor and analysis of binding to its receptor kit.

EMBO J, 19, 3192-3203.

PDB code: 1scf

10489458 C.Kasper, H.Rasmussen, V.Berezin, E.Bock, and I.K.Larsen (1999).
Expression, crystallization and preliminary X-ray analysis of the two amino-terminal Ig domains of the neural cell adhesion molecule (NCAM).

Acta Crystallogr D Biol Crystallogr, 55, 1598-1600.

10442767 F.Peri, D.Grell, P.Dumy, Y.Yokokawa, K.Welzenbach, G.Weitz-Schmidt, and M.Mutter (1999).
Assembly of binding loops on aromatic templates as VCAM-1 mimetics.

J Pept Sci, 5, 313-322.

10077629 J.M.Casasnovas, C.Pieroni, and T.A.Springer (1999).
Lymphocyte function-associated antigen-1 binding residues in intercellular adhesion molecule-2 (ICAM-2) and the integrin binding surface in the ICAM subfamily.

Proc Natl Acad Sci U S A, 96, 3017-3022.

9889186 M.Bycroft, A.Bateman, J.Clarke, S.J.Hamill, R.Sandford, R.L.Thomas, and C.Chothia (1999).
The structure of a PKD domain from polycystin-1: implications for polycystic kidney disease.

EMBO J, 18, 297-305.

PDB code: 1b4r

10457201 R.W.Berg, Y.Yang, K.Lehnert, and G.W.Krissansen (1999).
Mouse M290 is the functional homologue of the human mucosal lymphocyte integrin HML-1: antagonism between the integrin ligands E-cadherin and RGD tripeptide.

Immunol Cell Biol, 77, 337-344.

10036968 C.Quan, N.J.Skelton, K.Clark, D.Y.Jackson, M.E.Renz, H.H.Chiu, S.M.Keating, M.H.Beresini, S.Fong, and D.R.Artis (1998).
Transfer of a protein binding epitope to a minimal designed peptide.

Biopolymers, 47, 265-275.

9700498 I.D.Campbell (1998).
The modular architecture of leukocyte cell-surface receptors.

Immunol Rev, 163, 11-18.

9539703 J.Bella, P.R.Kolatkar, C.W.Marlor, J.M.Greve, and M.G.Rossmann (1998).
The structure of the two amino-terminal domains of human ICAM-1 suggests how it functions as a rhinovirus receptor and as an LFA-1 integrin ligand.

Proc Natl Acad Sci U S A, 95, 4140-4145.

PDB code: 1iam

9733775 J.L.Banères, F.Roquet, M.Green, H.LeCalvez, and J.Parello (1998).
The cation-binding domain from the alpha subunit of integrin alpha5 beta1 is a minimal domain for fibronectin recognition.

J Biol Chem, 273, 24744-24753.

9539702 J.M.Casasnovas, T.Stehle, J.H.Liu, J.H.Wang, and T.A.Springer (1998).
A dimeric crystal structure for the N-terminal two domains of intercellular adhesion molecule-1.

Proc Natl Acad Sci U S A, 95, 4134-4139.

PDB code: 1ic1

9425167 J.M.Higgins, D.A.Mandlebrot, S.K.Shaw, G.J.Russell, E.A.Murphy, Y.T.Chen, W.J.Nelson, C.M.Parker, and M.B.Brenner (1998).
Direct and regulated interaction of integrin alphaEbeta7 with E-cadherin.

J Cell Biol, 140, 197-210.

9700512 J.Wang, and T.A.Springer (1998).
Structural specializations of immunoglobulin superfamily members for adhesion to integrins and viruses.

Immunol Rev, 163, 197-215.

9420281 N.Verdaguer, N.Sevilla, M.L.Valero, D.Stuart, E.Brocchi, D.Andreu, E.Giralt, E.Domingo, M.G.Mateu, and I.Fita (1998).
A similar pattern of interaction for different antibodies with a major antigenic site of foot-and-mouth disease virus: implications for intratypic antigenic variation.

J Virol, 72, 739-748.

9488719 R.Urfer, P.Tsoulfas, L.O'Connell, J.A.Hongo, W.Zhao, and L.G.Presta (1998).
High resolution mapping of the binding site of TrkA for nerve growth factor and TrkC for neurotrophin-3 on the second immunoglobulin-like domain of the Trk receptors.

J Biol Chem, 273, 5829-5840.

9417088 S.Ichikawa, H.Hatanaka, T.Yuuki, N.Iwamoto, S.Kojima, C.Nishiyama, K.Ogura, Y.Okumura, and F.Inagaki (1998).
Solution structure of Der f 2, the major mite allergen for atopic diseases.

J Biol Chem, 273, 356-360.

PDB codes: 1ahk 1ahm

9700513 S.J.Davis, S.Ikemizu, M.K.Wild, and P.A.van der Merwe (1998).
CD2 and the nature of protein interactions mediating cell-cell recognition.

Immunol Rev, 163, 217-236.

9565552 Y.Yokosaki, N.Matsuura, S.Higashiyama, I.Murakami, M.Obara, M.Yamakido, N.Shigeto, J.Chen, and D.Sheppard (1998).
Identification of the ligand binding site for the integrin alpha9 beta1 in the third fibronectin type III repeat of tenascin-C.

J Biol Chem, 273, 11423-11428.

9070454 A.P.May, R.C.Robinson, R.T.Aplin, P.Bradfield, P.R.Crocker, and E.Y.Jones (1997).
Expression, crystallization, and preliminary X-ray analysis of a sialic acid-binding fragment of sialoadhesin in the presence and absence of ligand.

Protein Sci, 6, 717-721.

9242926 C.Chothia, and E.Y.Jones (1997).
The molecular structure of cell adhesion molecules.

Annu Rev Biochem, 66, 823-862.

9151947 C.G.Gahmberg, M.Tolvanen, and P.Kotovuori (1997).
Leukocyte adhesion--structure and function of human leukocyte beta2-integrins and their cellular ligands.

Eur J Biochem, 245, 215-232.

9442878 D.J.Leahy (1997).
Implications of atomic-resolution structures for cell adhesion.

Annu Rev Cell Dev Biol, 13, 363-393.

9053451 D.L.Bodian, S.J.Davis, B.P.Morgan, and N.K.Rushmere (1997).
Mutational analysis of the active site and antibody epitopes of the complement-inhibitory glycoprotein, CD59.

J Exp Med, 185, 507-516.

9343347 E.Domingo, and J.J.Holland (1997).
RNA virus mutations and fitness for survival.

Annu Rev Microbiol, 51, 151-178.

9153268 J.C.Loftus, and R.C.Liddington (1997).
Cell adhesion in vascular biology. New insights into integrin-ligand interaction.

J Clin Invest, 99, 2302-2306.

9252369 J.P.Newton, C.D.Buckley, E.Y.Jones, and D.L.Simmons (1997).
Residues on both faces of the first immunoglobulin fold contribute to homophilic binding sites of PECAM-1/CD31.

J Biol Chem, 272, 20555-20563.

9188101 K.L.Fisher, J.Lu, L.Riddle, K.J.Kim, L.G.Presta, and S.C.Bodary (1997).
Identification of the binding site in intercellular adhesion molecule 1 for its receptor, leukocyte function-associated antigen 1.

Mol Biol Cell, 8, 501-515.

9235944 P.Newham, S.E.Craig, G.N.Seddon, N.R.Schofield, A.Rees, R.M.Edwards, E.Y.Jones, and M.J.Humphries (1997).
Alpha4 integrin binding interfaces on VCAM-1 and MAdCAM-1. Integrin binding footprints identify accessory binding sites that play a role in integrin specificity.

J Biol Chem, 272, 19429-19440.

9342427 R.J.Gumina, P.J.Newman, D.Kenny, D.C.Warltier, and G.J.Gross (1997).
The leukocyte cell adhesion cascade and its role in myocardial ischemia-reperfusion injury.

Basic Res Cardiol, 92, 201-213.

9379078 S.Fong, S.Jones, M.E.Renz, H.H.Chiu, A.M.Ryan, L.G.Presta, and D.Jackson (1997).
Mucosal addressin cell adhesion molecule-1 (MAdCAM-1). Its binding motif for alpha 4 beta 7 and role in experimental colitis.

Immunol Res, 16, 299-311.

9150458 T.Sugimori, D.L.Griffith, and M.A.Arnaout (1997).
Emerging paradigms of integrin ligand binding and activation.

Kidney Int, 51, 1454-1462.

8947027 A.Bateman, M.Jouet, J.MacFarlane, J.S.Du, S.Kenwrick, and C.Chothia (1996).
Outline structure of the human L1 cell adhesion molecule and the sites where mutations cause neurological disorders.

EMBO J, 15, 6050-6059.

8880921 A.Bateman, S.R.Eddy, and C.Chothia (1996).
Members of the immunoglobulin superfamily in bacteria.

Protein Sci, 5, 1939-1941.

8648715 A.K.Basak, P.Gouet, J.Grimes, P.Roy, and D.Stuart (1996).
Crystal structure of the top domain of African horse sickness virus VP7: comparisons with bluetongue virus VP7.

J Virol, 70, 3797-3806.

PDB code: 1ahs

8823162 J.E.Skonier, M.A.Bowen, J.Emswiler, A.Aruffo, and J.Bajorath (1996).
Recognition of diverse proteins by members of the immunoglobulin superfamily: delineation of the receptor binding site in the human CD6 ligand ALCAM.

Biochemistry, 35, 12287-12291.

8973654 J.H.Viles, J.B.Mitchell, S.L.Gough, P.M.Doyle, C.J.Harris, P.J.Sadler, and J.M.Thornton (1996).
Multiple solution conformations of the integrin-binding cyclic pentapeptide cyclo(-Ser-D-Leu-Asp-Val-Pro-). Analysis of the (phi, psi) space available to cyclic pentapeptides.

Eur J Biochem, 242, 352-362.

8798624 L.B.Klickstein, M.R.York, A.R.Fougerolles, and T.A.Springer (1996).
Localization of the binding site on intercellular adhesion molecule-3 (ICAM-3) for lymphocyte function-associated antigen 1 (LFA-1).

J Biol Chem, 271, 23920-23927.

8970726 M.Raghavan, and P.J.Bjorkman (1996).
Fc receptors and their interactions with immunoglobulins.

Annu Rev Cell Dev Biol, 12, 181-220.

8673600 N.K.Thomsen, V.Soroka, P.H.Jensen, V.Berezin, V.V.Kiselyov, E.Bock, and F.M.Poulsen (1996).
The three-dimensional structure of the first domain of neural cell adhesion molecule.

Nat Struct Biol, 3, 581-585.

PDB codes: 1ncm 2ncm

8870072 P.Bork, A.K.Downing, B.Kieffer, and I.D.Campbell (1996).
Structure and distribution of modules in extracellular proteins.

Q Rev Biophys, 29, 119-167.

8981082 S.Kelm, R.Schauer, and P.R.Crocker (1996).
The Sialoadhesins--a family of sialic acid-dependent cellular recognition molecules within the immunoglobulin superfamily.

Glycoconj J, 13, 913-926.

8846218 A.Bateman, and C.Chothia (1995).
Outline structures for the extracellular domains of the fibroblast growth factor receptors.

Nat Struct Biol, 2, 1068-1074.

7642561 C.Huang, and T.A.Springer (1995).
A binding interface on the I domain of lymphocyte function-associated antigen-1 (LFA-1) required for specific interaction with intercellular adhesion molecule 1 (ICAM-1).

J Biol Chem, 270, 19008-19016.

8520490 J.Bajorath, M.A.Bowen, and A.Aruffo (1995).
Molecular model of the N-terminal receptor-binding domain of the human CD6 ligand ALCAM.

Protein Sci, 4, 1644-1647.

PDB code: 1kjc

7663510 J.Hughes, C.J.Ward, B.Peral, R.Aspinwall, K.Clark, J.L.San Millán, V.Gamble, and P.C.Harris (1995).
The polycystic kidney disease 1 (PKD1) gene encodes a novel protein with multiple cell recognition domains.

Nat Genet, 10, 151-160.

7595194 J.Miller, R.Knorr, M.Ferrone, R.Houdei, C.P.Carron, and M.L.Dustin (1995).
Intercellular adhesion molecule-1 dimerization and its consequences for adhesion mediated by lymphocyte function associated-1.

J Exp Med, 182, 1231-1241.

7624321 L.Shapiro, P.D.Kwong, A.M.Fannon, D.R.Colman, and W.A.Hendrickson (1995).
Considerations on the folding topology and evolutionary origin of cadherin domains.

Proc Natl Acad Sci U S A, 92, 6793-6797.

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.