PDBsum entry 1f97

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protein metals links
Cell adhesion PDB id
Jmol PyMol
Protein chain
207 a.a. *
Waters ×70
* Residue conservation analysis
PDB id:
Name: Cell adhesion
Title: Soluble part of the junction adhesion molecule from mouse
Structure: Junction adhesion molecule. Chain: a. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9.
Biol. unit: Dimer (from PQS)
2.50Å     R-factor:   0.150     R-free:   0.210
Authors: D.Kostrewa,M.Brockhaus,A.D'Arcy,G.Dale,G.Bazzoni,E.Dejana, F.Winkler,M.Hennig
Key ref:
D.Kostrewa et al. (2001). X-ray structure of junctional adhesion molecule: structural basis for homophilic adhesion via a novel dimerization motif. EMBO J, 20, 4391-4398. PubMed id: 11500366 DOI: 10.1093/emboj/20.16.4391
07-Jul-00     Release date:   10-Jan-01    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
O88792  (JAM1_MOUSE) -  Junctional adhesion molecule A
300 a.a.
207 a.a.
Key:    PfamA domain  Secondary structure  CATH domain


DOI no: 10.1093/emboj/20.16.4391 EMBO J 20:4391-4398 (2001)
PubMed id: 11500366  
X-ray structure of junctional adhesion molecule: structural basis for homophilic adhesion via a novel dimerization motif.
D.Kostrewa, M.Brockhaus, A.D'Arcy, G.E.Dale, P.Nelboeck, G.Schmid, F.Mueller, G.Bazzoni, E.Dejana, T.Bartfai, F.K.Winkler, M.Hennig.
Junctional adhesion molecules (JAMs) are a family of immunoglobulin-like single-span transmembrane molecules that are expressed in endothelial cells, epithelial cells, leukocytes and myocardia. JAM has been suggested to contribute to the adhesive function of tight junctions and to regulate leukocyte trans migration. We describe the crystal structure of the recombinant extracellular part of mouse JAM (rsJAM) at 2.5 A resolution. rsJAM consists of two immunoglobulin-like domains that are connected by a conformationally restrained short linker. Two rsJAM molecules form a U-shaped dimer with highly complementary interactions between the N-terminal domains. Two salt bridges are formed in a complementary manner by a novel dimerization motif, R(V,I,L)E, which is essential for the formation of rsJAM dimers in solution and common to the known members of the JAM family. Based on the crystal packing and studies with mutant rsJAM, we propose a model for homophilic adhesion of JAM. In this model, U-shaped JAM dimers are oriented in cis on the cell surface and form a two-dimensional network by trans-interactions of their N-terminal domains with JAM dimers from an opposite cell surface.
  Selected figure(s)  
Figure 1.
Figure 1 Schematic picture of the structure of rsJAM. The N- and C-terminal domains are coloured in cyan and orange, and the short linker between the two domains is coloured in green. Both domains have an immunoglobulin-like fold of the variable type. The -strands are labelled according to the immunoglobulin convention. The disordered c' -c" hairpin in the C-terminal domain (Ala175 -Asp176 -Ala177 -Lys178 -Lys179) is indicated by a dashed line. Both disulfide bridges (Cys49 -Cys108 and Cys152 -C212) are shown in a yellow stick representation.
Figure 2.
Figure 2 Stereo view of the linker region Val127 -Leu128 -Val129 (green) between the N- (cyan) and C-terminal domain (orange) in a ball-and-stick representation. Oxygen and nitrogen atoms are coloured red and blue, respectively. The extensive hydrogen bond network between the main chain atoms of the linker tri-peptide and both domains is shown with black dotted lines. The side chain of Leu128 is tightly packed in a hydrophobic pocket formed by the side chains of Gln38, Pro40, Thr126, Pro159 and Tyr218. Several proline residues (Pro40, Pro130, Pro131, Pro159 and Pro160) stabilize the main chain conformation around the linker.
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2001, 20, 4391-4398) copyright 2001.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21372850 P.Nava, C.T.Capaldo, S.Koch, K.Kolegraff, C.R.Rankin, A.E.Farkas, M.E.Feasel, L.Li, C.Addis, C.A.Parkos, and A.Nusrat (2011).
JAM-A regulates epithelial proliferation through Akt/β-catenin signalling.
  EMBO Rep, 12, 314-320.  
  20536563 G.J.Freeman, J.M.Casasnovas, D.T.Umetsu, and R.H.DeKruyff (2010).
TIM genes: a family of cell surface phosphatidylserine receptors that regulate innate and adaptive immunity.
  Immunol Rev, 235, 172-189.  
20182541 O.J.Baker (2010).
Tight junctions in salivary epithelium.
  J Biomed Biotechnol, 2010, 278948.  
20444976 T.Padilla-Benavides, M.L.Roldán, I.Larre, D.Flores-Benitez, N.Villegas-Sepúlveda, R.G.Contreras, M.Cereijido, and L.Shoshani (2010).
The polarized distribution of Na+,K+-ATPase: role of the interaction between {beta} subunits.
  Mol Biol Cell, 21, 2217-2225.  
19538282 E.A.Severson, and C.A.Parkos (2009).
Mechanisms of outside-in signaling at the tight junction by junctional adhesion molecule A.
  Ann N Y Acad Sci, 1165, 10-18.  
19608396 E.A.Severson, and C.A.Parkos (2009).
Structural determinants of Junctional Adhesion Molecule A (JAM-A) function and mechanisms of intracellular signaling.
  Curr Opin Cell Biol, 21, 701-707.  
19176753 E.A.Severson, W.Y.Lee, C.T.Capaldo, A.Nusrat, and C.A.Parkos (2009).
Junctional adhesion molecule A interacts with Afadin and PDZ-GEF2 to activate Rap1A, regulate beta1 integrin levels, and enhance cell migration.
  Mol Biol Cell, 20, 1916-1925.  
  19652868 E.Chavakis, E.Y.Choi, and T.Chavakis (2009).
Novel aspects in the regulation of the leukocyte adhesion cascade.
  Thromb Haemost, 102, 191-197.  
19948502 E.Klaile, O.Vorontsova, K.Sigmundsson, M.M.Müller, B.B.Singer, L.G.Ofverstedt, S.Svensson, U.Skoglund, and B.Obrink (2009).
The CEACAM1 N-terminal Ig domain mediates cis- and trans-binding and is essential for allosteric rearrangements of CEACAM1 microclusters.
  J Cell Biol, 187, 553-567.  
19273217 E.S.Wittchen (2009).
Endothelial signaling in paracellular and transcellular leukocyte transmigration.
  Front Biosci, 14, 2522-2545.  
19273149 E.Y.Choi, S.Santoso, and T.Chavakis (2009).
Mechanisms of neutrophil transendothelial migration.
  Front Biosci, 14, 1596-1605.  
19538472 H.F.Langer, and T.Chavakis (2009).
Leukocyte-endothelial interactions in inflammation.
  J Cell Mol Med, 13, 1211-1220.  
19204148 S.Immenschuh, S.Naidu, T.Chavakis, H.Beschmann, R.J.Ludwig, and S.Santoso (2009).
Transcriptional induction of junctional adhesion molecule-C gene expression in activated T cells.
  J Leukoc Biol, 85, 796-803.  
19064666 A.C.Luissint, P.G.Lutz, D.A.Calderwood, P.O.Couraud, and S.Bourdoulous (2008).
JAM-L-mediated leukocyte adhesion to endothelial cells is regulated in cis by alpha4beta1 integrin activation.
  J Cell Biol, 183, 1159-1173.  
18821692 B.J.Rabquer, A.Pakozdi, J.E.Michel, B.S.Gujar, G.K.Haines, B.A.Imhof, and A.E.Koch (2008).
Junctional adhesion molecule C mediates leukocyte adhesion to rheumatoid arthritis synovium.
  Arthritis Rheum, 58, 3020-3029.  
18550656 D.Bhella, D.Gatherer, Y.Chaudhry, R.Pink, and I.G.Goodfellow (2008).
Structural insights into calicivirus attachment and uncoating.
  J Virol, 82, 8051-8058.  
18272784 E.A.Severson, L.Jiang, A.I.Ivanov, K.J.Mandell, A.Nusrat, and C.A.Parkos (2008).
Cis-dimerization mediates function of junctional adhesion molecule a.
  Mol Biol Cell, 19, 1862-1872.  
19079583 E.Kirchner, K.M.Guglielmi, H.M.Strauss, T.S.Dermody, and T.Stehle (2008).
Structure of reovirus sigma1 in complex with its receptor junctional adhesion molecule-A.
  PLoS Pathog, 4, e1000235.
PDB code: 3eoy
18667420 J.Xie, S.Reverdatto, A.Frolov, R.Hoffmann, D.S.Burz, and A.Shekhtman (2008).
Structural Basis for Pattern Recognition by the Receptor for Advanced Glycation End Products (RAGE).
  J Biol Chem, 283, 27255-27269.  
18236042 M.E.Ackerman, C.Chalouni, M.M.Schmidt, V.V.Raman, G.Ritter, L.J.Old, I.Mellman, and K.D.Wittrup (2008).
A33 antigen displays persistent surface expression.
  Cancer Immunol Immunother, 57, 1017-1027.  
18446885 S.R.Vedula, T.S.Lim, E.Kirchner, K.M.Guglielmi, T.S.Dermody, T.Stehle, W.Hunziker, and C.T.Lim (2008).
A comparative molecular force spectroscopy study of homophilic JAM-A interactions and JAM-A interactions with reovirus attachment protein sigma1.
  J Mol Recognit, 21, 210-216.  
  19262151 U.P.Naik, and M.U.Naik (2008).
Putting the brakes on cancer cell migration: JAM-A restrains integrin activation.
  Cell Adh Migr, 2, 249-251.  
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
18506084 Y.Yoshikumi, H.Ohno, J.Suzuki, M.Isshiki, Y.Morishita, H.Ohnishi, H.Yasuda, M.Omata, T.Fujita, and H.Mashima (2008).
Up-regulation of JAM-1 in AR42J cells treated with activin A and betacellulin and the diabetic regenerating islets.
  Endocr J, 55, 757-765.  
17109403 A.Krisko, and C.Etchebest (2007).
Theoretical model of human apolipoprotein B100 tertiary structure.
  Proteins, 66, 342-358.  
17935964 A.R.Aricescu, and E.Y.Jones (2007).
Immunoglobulin superfamily cell adhesion molecules: zippers and signals.
  Curr Opin Cell Biol, 19, 543-550.  
17363299 C.Santiago, A.Ballesteros, C.Tami, L.Martínez-Muñoz, G.G.Kaplan, and J.M.Casasnovas (2007).
Structures of T Cell immunoglobulin mucin receptors 1 and 2 reveal mechanisms for regulation of immune responses by the TIM receptor family.
  Immunity, 26, 299-310.
PDB codes: 2or7 2or8
17525755 C.Weber, L.Fraemohs, and E.Dejana (2007).
The role of junctional adhesion molecules in vascular inflammation.
  Nat Rev Immunol, 7, 467-477.  
17624953 D.Vestweber (2007).
Adhesion and signaling molecules controlling the transmigration of leukocytes through endothelium.
  Immunol Rev, 218, 178-196.  
17724169 K.J.Mandell, L.Berglin, E.A.Severson, H.F.Edelhauser, and C.A.Parkos (2007).
Expression of JAM-A in the human corneal endothelium and retinal pigment epithelium: localization and evidence for role in barrier function.
  Invest Ophthalmol Vis Sci, 48, 3928-3936.  
17452315 K.M.Guglielmi, E.Kirchner, G.H.Holm, T.Stehle, and T.S.Dermody (2007).
Reovirus binding determinants in junctional adhesion molecule-A.
  J Biol Chem, 282, 17930-17940.  
17502225 L.González-Mariscal, S.Lechuga, and E.Garay (2007).
Role of tight junctions in cell proliferation and cancer.
  Prog Histochem Cytochem, 42, 1.  
17913818 R.J.Ossiboff, and J.S.Parker (2007).
Identification of regions and residues in feline junctional adhesion molecule required for feline calicivirus binding and infection.
  J Virol, 81, 13608-13621.  
16771626 K.Shin, V.C.Fogg, and B.Margolis (2006).
Tight junctions and cell polarity.
  Annu Rev Cell Dev Biol, 22, 207-235.  
16914739 T.Sakaguchi, M.Nishimoto, S.Miyagi, A.Iwama, Y.Morita, N.Iwamori, H.Nakauchi, H.Kiyonari, M.Muramatsu, and A.Okuda (2006).
Putative "stemness" gene jam-B is not required for maintenance of stem cell state in embryonic, neural, or hematopoietic stem cells.
  Mol Cell Biol, 26, 6557-6570.  
16467305 X.Dong, F.Xu, Y.Gong, J.Gao, P.Lin, T.Chen, Y.Peng, B.Qiang, J.Yuan, X.Peng, and Z.Rao (2006).
Crystal structure of the V domain of human Nectin-like molecule-1/Syncam3/Tsll1/Igsf4b, a neural tissue-specific immunoglobulin-like cell-cell adhesion molecule.
  J Biol Chem, 281, 10610-10617.
PDB code: 1z9m
16093349 C.Lamagna, P.Meda, G.Mandicourt, J.Brown, R.J.Gilbert, E.Y.Jones, F.Kiefer, P.Ruga, B.A.Imhof, and M.Aurrand-Lions (2005).
Dual interaction of JAM-C with JAM-B and alpha(M)beta2 integrin: function in junctional complexes and leukocyte adhesion.
  Mol Biol Cell, 16, 4992-5003.  
15956543 J.A.Campbell, P.Schelling, J.D.Wetzel, E.M.Johnson, J.C.Forrest, G.A.Wilson, M.Aurrand-Lions, B.A.Imhof, T.Stehle, and T.S.Dermody (2005).
Junctional adhesion molecule a serves as a receptor for prototype and field-isolate strains of mammalian reovirus.
  J Virol, 79, 7967-7978.  
15677455 K.J.Mandell, B.A.Babbin, A.Nusrat, and C.A.Parkos (2005).
Junctional adhesion molecule 1 regulates epithelial cell morphology through effects on beta1 integrins and Rap1 activity.
  J Biol Chem, 280, 11665-11674.  
15800062 K.Zen, Y.Liu, I.C.McCall, T.Wu, W.Lee, B.A.Babbin, A.Nusrat, and C.A.Parkos (2005).
Neutrophil migration across tight junctions is mediated by adhesive interactions between epithelial coxsackie and adenovirus receptor and a junctional adhesion molecule-like protein on neutrophils.
  Mol Biol Cell, 16, 2694-2703.  
15953183 L.Du Pasquier (2005).
Meeting the demand for innate and adaptive immunities during evolution.
  Scand J Immunol, 62, 39-48.  
16296754 P.H.Johnson, and S.C.Quay (2005).
Advances in nasal drug delivery through tight junction technology.
  Expert Opin Drug Deliv, 2, 281-298.  
16118203 S.Santoso, V.V.Orlova, K.Song, U.J.Sachs, C.L.Andrei-Selmer, and T.Chavakis (2005).
The homophilic binding of junctional adhesion molecule-C mediates tumor cell-endothelial cell interactions.
  J Biol Chem, 280, 36326-36333.  
16045455 V.V.Kiselyov, V.Soroka, V.Berezin, and E.Bock (2005).
Structural biology of NCAM homophilic binding and activation of FGFR.
  J Neurochem, 94, 1169-1179.  
14623883 C.Heiring, B.Dahlbäck, and Y.A.Muller (2004).
Ligand recognition and homophilic interactions in Tyro3: structural insights into the Axl/Tyro3 receptor tyrosine kinase family.
  J Biol Chem, 279, 6952-6958.
PDB code: 1rhf
14749337 K.J.Mandell, I.C.McCall, and C.A.Parkos (2004).
Involvement of the junctional adhesion molecule-1 (JAM1) homodimer interface in regulation of epithelial barrier function.
  J Biol Chem, 279, 16254-16262.  
15199966 L.Du Pasquier, I.Zucchetti, and R.De Santis (2004).
Immunoglobulin superfamily receptors in protochordates: before RAG time.
  Immunol Rev, 198, 233-248.  
  15343392 M.R.Cera, A.Del Prete, A.Vecchi, M.Corada, I.Martin-Padura, T.Motoike, P.Tonetti, G.Bazzoni, W.Vermi, F.Gentili, S.Bernasconi, T.N.Sato, A.Mantovani, and E.Dejana (2004).
Increased DC trafficking to lymph nodes and contact hypersensitivity in junctional adhesion molecule-A-deficient mice.
  J Clin Invest, 114, 729-738.  
14685273 S.J.Parkinson, J.A.Le Good, R.D.Whelan, P.Whitehead, and P.J.Parker (2004).
Identification of PKCzetaII: an endogenous inhibitor of cell polarity.
  EMBO J, 23, 77-88.  
15279694 T.Stehle, and T.S.Dermody (2004).
Structural similarities in the cellular receptors used by adenovirus and reovirus.
  Viral Immunol, 17, 129-143.  
12697893 A.E.Prota, J.A.Campbell, P.Schelling, J.C.Forrest, M.J.Watson, T.R.Peters, M.Aurrand-Lions, B.A.Imhof, T.S.Dermody, and T.Stehle (2003).
Crystal structure of human junctional adhesion molecule 1: implications for reovirus binding.
  Proc Natl Acad Sci U S A, 100, 5366-5371.
PDB code: 1nbq
12960396 C.S.Clements, H.H.Reid, T.Beddoe, F.E.Tynan, M.A.Perugini, T.G.Johns, C.C.Bernard, and J.Rossjohn (2003).
The crystal structure of myelin oligodendrocyte glycoprotein, a key autoantigen in multiple sclerosis.
  Proc Natl Acad Sci U S A, 100, 11059-11064.
PDB code: 1py9
12805421 E.Wu, L.Pache, D.J.Von Seggern, T.M.Mullen, Y.Mikyas, P.L.Stewart, and G.R.Nemerow (2003).
Flexibility of the adenovirus fiber is required for efficient receptor interaction.
  J Virol, 77, 7225-7235.  
14519386 G.Bazzoni (2003).
The JAM family of junctional adhesion molecules.
  Curr Opin Cell Biol, 15, 525-530.  
12529374 I.Kalus, B.Schnegelsberg, N.G.Seidah, R.Kleene, and M.Schachner (2003).
The proprotein convertase PC5A and a metalloprotease are involved in the proteolytic processing of the neural adhesion molecule L1.
  J Biol Chem, 278, 10381-10388.  
12966102 J.C.Forrest, J.A.Campbell, P.Schelling, T.Stehle, and T.S.Dermody (2003).
Structure-function analysis of reovirus binding to junctional adhesion molecule 1. Implications for the mechanism of reovirus attachment.
  J Biol Chem, 278, 48434-48444.  
12940823 M.Tajima, S.Hirabayashi, I.Yao, M.Shirasawa, J.Osuga, S.Ishibashi, T.Fujita, and Y.Hata (2003).
Roles of immunoglobulin-like loops of junctional cell adhesion molecule 4; involvement in the subcellular localization and the cell adhesion.
  Genes Cells, 8, 759-768.  
12627395 T.Stehle, and T.S.Dermody (2003).
Structural evidence for common functions and ancestry of the reovirus and adenovirus attachment proteins.
  Rev Med Virol, 13, 123-132.  
12231354 D.Vestweber (2002).
Regulation of endothelial cell contacts during leukocyte extravasation.
  Curr Opin Cell Biol, 14, 587-593.  
12234362 F.W.Luscinskas, S.Ma, A.Nusrat, C.A.Parkos, and S.K.Shaw (2002).
The role of endothelial cell lateral junctions during leukocyte trafficking.
  Immunol Rev, 186, 57-67.  
11978082 F.W.Luscinskas, S.Ma, A.Nusrat, C.A.Parkos, and S.K.Shaw (2002).
Leukocyte transendothelial migration: a junctional affair.
  Semin Immunol, 14, 105-113.  
11782420 J.D.Chappell, A.E.Prota, T.S.Dermody, and T.Stehle (2002).
Crystal structure of reovirus attachment protein sigma1 reveals evolutionary relationship to adenovirus fiber.
  EMBO J, 21, 1.
PDB code: 1kke
12070135 S.A.Cunningham, J.M.Rodriguez, M.P.Arrate, T.M.Tran, and T.A.Brock (2002).
JAM2 interacts with alpha4beta1. Facilitation by JAM3.
  J Biol Chem, 277, 27589-27592.  
12011057 S.Fabre, N.Reymond, F.Cocchi, L.Menotti, P.Dubreuil, G.Campadelli-Fiume, and M.Lopez (2002).
Prominent role of the Ig-like V domain in trans-interactions of nectins. Nectin3 and nectin 4 bind to the predicted C-C'-C"-D beta-strands of the nectin1 V domain.
  J Biol Chem, 277, 27006-27013.  
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.