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protein ligands metals Protein-protein interface(s) links
Structural protein PDB id
1q5a
Jmol
Contents
Protein chains
540 a.a. *
Ligands
NAG ×22
NDG ×8
Metals
_CA ×24
* Residue conservation analysis
PDB id:
1q5a
Name: Structural protein
Title: S-shaped trans interactions of cadherins model based on fitt cadherin (1l3w) to 3d map of desmosomes obtained by electro tomography
Structure: Ep-cadherin. Chain: a, b. Fragment: residues 1-546 of PDB entry 1l3w. Synonym: c-cadherin. Other_details: rigid body fit by c-cadherin from PDB entry
Source: Mus musculus. House mouse. Organism_taxid: 10090. Tissue: skin. Other_details: desmosome preparation from newborn mouse ski
Biol. unit: Dimer (from PQS)
Authors: W.He,P.Cowin,D.L.Stokes
Key ref:
W.He et al. (2003). Untangling desmosomal knots with electron tomography. Science, 302, 109-113. PubMed id: 14526082 DOI: 10.1126/science.1086957
Date:
06-Aug-03     Release date:   07-Oct-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   3 terms 
  Biological process     cell adhesion   2 terms 
  Biochemical function     calcium ion binding     1 term  

 

 
DOI no: 10.1126/science.1086957 Science 302:109-113 (2003)
PubMed id: 14526082  
 
 
Untangling desmosomal knots with electron tomography.
W.He, P.Cowin, D.L.Stokes.
 
  ABSTRACT  
 
Cell adhesion by adherens junctions and desmosomes relies on interactions between cadherin molecules. However, the molecular interfaces that define molecular specificity and that mediate adhesion remain controversial. We used electron tomography of plastic sections from neonatal mouse skin to visualize the organization of desmosomes in situ. The resulting three-dimensional maps reveal individual cadherin molecules forming discrete groups and interacting through their tips. Fitting of an x-ray crystal structure for C-cadherin to these maps is consistent with a flexible intermolecular interface mediated by an exchange of amino-terminal tryptophans. This flexibility suggests a novel mechanism for generating both cis and trans interactions and for propagating these adhesive interactions along the junction.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Images of desmosomes from neonatal mouse epidermis. (A) Low-magnification image showing an irregular border between keratinocytes coupled by frequent desmosomes. This region of the cell contains many ribosomes but, if the opaque discs are construed as en face views of desmosomes, lacks organelles. (B to D) Higher magnification images reveal the typical lamellar structure of desmosomes. The membrane appears as a narrow white zone; cadherin molecules appear as strands crossing the extracellular space, which is bisected by an electron-dense midline. Individual cadherins are difficult to identify because of extensive superposition of these densely packed molecules within the section; individual molecules are more readily seen in ultrathin sections that are unsuitable for tomography but are included in (13). A very dense plaque abuts the intracellular face of the membrane and leads to a looser network of fibrous densities that ultimately connect to bundles of intermediate filaments. (E and F) Sections through the tomographic reconstruction of desmosome "R" (see Table 1) cut parallel (E) and perpendicular (F) to the untilted sample [e.g., (B)]. The membrane is outlined in red, cadherin molecules in blue, two zones of the cytoplasmic plaque in orange and light green, and intermediate filaments in dark green. The perpendicular section in (F) reveals the thickness of the plastic section and illustrates that the resolution was quite isotropic [see also (13)]. Scale bars, 500 nm (A), 100 nm [(B) to (D)], 30 nm [(E) and (F)]. 		Figure 2.
Fig. 2. Delineation and fitting of cadherin molecules to the desmosome. With the C-cadherin x-ray structure as a template, 136 cadherin molecules were delineated in the region of desmosome "P" (see Table 1). (A) Densities from the map, with individual cadherin molecules in various colors and the membrane in cyan. (B) A representative group of cadherin molecules clustering at the midline and interacting predominantly at their tips. (C to E) Three recurrent molecular interactions within the molecular groups, referred to as W, S, and , respectively. The x-ray structure for C-cadherin was fitted as a rigid body with no changes within the structure itself. (G to I) The resulting juxtaposition of EC1 domains, where each molecule has a distinct ribbon color, calcium ions are brown, the space-filling representation of the Trp2 side chain is dark orange, and the HAV sequence has a light orange ribbon with stick-like side chains.
 
  The above figures are reprinted by permission from the AAAs: Science (2003, 302, 109-113) copyright 2003.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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19616642 C.K.Fung, K.Seiffert-Sinha, K.W.Lai, R.Yang, D.Panyard, J.Zhang, N.Xi, and A.A.Sinha (2010).
Investigation of human keratinocyte cell adhesion using atomic force microscopy.
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20671997 D.Garrod (2010).
Desmosomes in vivo.
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Exploring the Nature of Desmosomal Cadherin Associations in 3D.
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Intercellular junction assembly, dynamics, and homeostasis.
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21038359 L.A.Chtcheglova, L.Wildling, J.Waschke, D.Drenckhahn, and P.Hinterdorfer (2010).
AFM functional imaging on vascular endothelial cells.
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20190754 O.J.Harrison, F.Bahna, P.S.Katsamba, X.Jin, J.Brasch, J.Vendome, G.Ahlsen, K.J.Carroll, S.R.Price, B.Honig, and L.Shapiro (2010).
Two-step adhesive binding by classical cadherins.
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PDB codes: 3lnd 3lne 3lnf 3lng 3lnh 3lni
20571587 T.J.Harris, and U.Tepass (2010).
Adherens junctions: from molecules to morphogenesis.
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20876147 Y.Wu, X.Jin, O.Harrison, L.Shapiro, B.H.Honig, and A.Ben-Shaul (2010).
Cooperativity between trans and cis interactions in cadherin-mediated junction formation.
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Characterization of multiple stable conformers of the EC5 domain of E-cadherin and the interaction of EC5 with E-cadherin peptides.
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Structure and biochemistry of cadherins and catenins.
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19500675 M.L.Dustin (2009).
Supported bilayers at the vanguard of immune cell activation studies.
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19199298 M.Trivedi, R.A.Davis, Y.Shabaik, A.Roy, G.Verkhivker, J.S.Laurence, C.R.Middaugh, and T.J.Siahaan (2009).
The role of covalent dimerization on the physical and chemical stability of the EC1 domain of human E-cadherin.
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18848899 P.Hulpiau, and F.van Roy (2009).
Molecular evolution of the cadherin superfamily.
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19164289 W.M.Heupel, T.Müller, A.Efthymiadis, E.Schmidt, D.Drenckhahn, and J.Waschke (2009).
Peptides Targeting the Desmoglein 3 Adhesive Interface Prevent Autoantibody-induced Acantholysis in Pemphigus.
  J Biol Chem, 284, 8589-8595.  
19037235 X.Mao, E.J.Choi, and A.S.Payne (2009).
Disruption of desmosome assembly by monovalent human pemphigus vulgaris monoclonal antibodies.
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19114658 Y.Zhang, S.Sivasankar, W.J.Nelson, and S.Chu (2009).
Resolving cadherin interactions and binding cooperativity at the single-molecule level.
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19734674 Y.Zhang, Y.Zhou, J.Zhu, S.Dong, C.Li, and Q.Xiang (2009).
Effect of a novel recombinant protein of fibronectinIII7-10/cadherin 11 EC1-2 on osteoblastic adhesion and differentiation.
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18496566 D.Acehan, C.Petzold, I.Gumper, D.D.Sabatini, E.J.Müller, P.Cowin, and D.L.Stokes (2008).
Plakoglobin is required for effective intermediate filament anchorage to desmosomes.
  J Invest Dermatol, 128, 2665-2675.  
18795316 D.Studer, B.M.Humbel, and M.Chiquet (2008).
Electron microscopy of high pressure frozen samples: bridging the gap between cellular ultrastructure and atomic resolution.
  Histochem Cell Biol, 130, 877-889.  
17707657 E.Salvi, F.Cantele, L.Zampighi, N.Fain, G.Pigino, G.Zampighi, and S.Lanzavecchia (2008).
JUST (Java User Segmentation Tool) for semi-automatic segmentation of tomographic maps.
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18421501 M.Auer, A.J.Koster, U.Ziese, C.Bajaj, N.Volkmann, d.a. .N.Wang, and A.J.Hudspeth (2008).
Three-dimensional architecture of hair-bundle linkages revealed by electron-microscopic tomography.
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The allosteric role of the Ca2+ switch in adhesion and elasticity of C-cadherin.
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18395225 S.Posy, L.Shapiro, and B.Honig (2008).
Sequence and structural determinants of strand swapping in cadherin domains: do all cadherins bind through the same adhesive interface?
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18682221 V.Z.Miloushev, F.Bahna, C.Ciatto, G.Ahlsen, B.Honig, L.Shapiro, and A.G.Palmer (2008).
Dynamic properties of a type II cadherin adhesive domain: implications for the mechanism of strand-swapping of classical cadherins.
  Structure, 16, 1195-1205.  
18818657 W.He, M.S.Ladinsky, K.E.Huey-Tubman, G.J.Jensen, J.R.McIntosh, and P.J.Björkman (2008).
FcRn-mediated antibody transport across epithelial cells revealed by electron tomography.
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Water at the surfaces of aligned phospholipid multibilayer model membranes probed with ultrafast vibrational spectroscopy.
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18719945 Z.M.Ahmed, S.Riazuddin, S.Aye, R.A.Ali, H.Venselaar, S.Anwar, P.P.Belyantseva, M.Qasim, S.Riazuddin, and T.B.Friedman (2008).
Gene structure and mutant alleles of PCDH15: nonsyndromic deafness DFNB23 and type 1 Usher syndrome.
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18064004 A.Al-Amoudi, D.C.Díez, M.J.Betts, and A.S.Frangakis (2007).
The molecular architecture of cadherins in native epidermal desmosomes.
  Nature, 450, 832-837.  
17761881 A.R.Aricescu, C.Siebold, K.Choudhuri, V.T.Chang, W.Lu, S.J.Davis, P.A.van der Merwe, and E.Y.Jones (2007).
Structure of a tyrosine phosphatase adhesive interaction reveals a spacer-clamp mechanism.
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PDB code: 2v5y
17945476 D.L.Stokes (2007).
Desmosomes from a structural perspective.
  Curr Opin Cell Biol, 19, 565-571.  
17850815 E.Parisini, J.M.Higgins, J.H.Liu, M.B.Brenner, and J.H.Wang (2007).
The crystal structure of human E-cadherin domains 1 and 2, and comparison with other cadherins in the context of adhesion mechanism.
  J Mol Biol, 373, 401-411.
PDB code: 2o72
17129736 F.Cantele, L.Zampighi, M.Radermacher, G.Zampighi, and S.Lanzavecchia (2007).
Local refinement: an attempt to correct for shrinkage and distortion in electron tomography.
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16973404 J.Engel (2007).
Visions for novel biophysical elucidations of extracellular matrix networks.
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17657525 J.Waschke, C.Menendez-Castro, P.Bruggeman, R.Koob, M.Amagai, H.J.Gruber, D.Drenckhahn, and W.Baumgartner (2007).
Imaging and force spectroscopy on desmoglein 1 using atomic force microscopy reveal multivalent Ca(2+)-dependent, low-affinity trans-interaction.
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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.  
17539752 S.Pokutta, and W.I.Weis (2007).
Structure and mechanism of cadherins and catenins in cell-cell contacts.
  Annu Rev Cell Dev Biol, 23, 237-261.  
17723309 W.He, C.Kivork, S.Machinani, M.K.Morphew, A.M.Gail, D.B.Tesar, N.E.Tiangco, J.R.McIntosh, and P.J.Bjorkman (2007).
A freeze substitution fixation-based gold enlarging technique for EM studies of endocytosed Nanogold-labeled molecules.
  J Struct Biol, 160, 103-113.  
16337695 A.M.Craig, E.R.Graf, and M.W.Linhoff (2006).
How to build a central synapse: clues from cell culture.
  Trends Neurosci, 29, 8.  
16834557 D.Leckband, and A.Prakasam (2006).
Mechanism and dynamics of cadherin adhesion.
  Annu Rev Biomed Eng, 8, 259-287.  
16980367 F.Cailliez, and R.Lavery (2006).
Dynamics and stability of E-cadherin dimers.
  Biophys J, 91, 3964-3971.  
16319177 O.Thoumine, M.Lambert, R.M.Mège, and D.Choquet (2006).
Regulation of N-cadherin dynamics at neuronal contacts by ligand binding and cytoskeletal coupling.
  Mol Biol Cell, 17, 862-875.  
16770573 P.John, M.Tariq, M.Arshad Rafiq, M.Amin-Ud-Din, D.Muhammad, I.Waheed, M.Ansar, and W.Ahmad (2006).
Recurrent intragenic deletion mutation in desmoglein 4 gene underlies autosomal recessive hypotrichosis in two Pakistani families of Balochi and Sindhi origins.
  Arch Dermatol Res, 298, 135-137.  
16564015 S.D.Patel, C.Ciatto, C.P.Chen, F.Bahna, M.Rajebhosale, N.Arkus, I.Schieren, T.M.Jessell, B.Honig, S.R.Price, and L.Shapiro (2006).
Type II cadherin ectodomain structures: implications for classical cadherin specificity.
  Cell, 124, 1255-1268.
PDB codes: 1zvn 1zxk 2a4c 2a4e 2a62
17057715 Z.Lin, S.Sriskanthadevan, H.Huang, C.H.Siu, and D.Yang (2006).
Solution structures of the adhesion molecule DdCAD-1 reveal new insights into Ca(2+)-dependent cell-cell adhesion.
  Nat Struct Mol Biol, 13, 1016-1022.
PDB codes: 1yhp 2b1o
15816835 A.Al-Amoudi, J.Dubochet, and L.Norlén (2005).
Nanostructure of the epidermal extracellular space as observed by cryo-electron microscopy of vitreous sections of human skin.
  J Invest Dermatol, 124, 764-777.  
15854040 A.Shimizu, A.Ishiko, T.Ota, H.Saito, H.Oka, K.Tsunoda, M.Amagai, and T.Nishikawa (2005).
In vivo ultrastructural localization of the desmoglein 3 adhesive interface to the desmosome mid-line.
  J Invest Dermatol, 124, 984-989.  
16025097 B.M.Gumbiner (2005).
Regulation of cadherin-mediated adhesion in morphogenesis.
  Nat Rev Mol Cell Biol, 6, 622-634.  
16106450 P.Lupetti, S.Lanzavecchia, D.Mercati, F.Cantele, R.Dallai, and C.Mencarelli (2005).
Three-dimensional reconstruction of axonemal outer dynein arms in situ by electron tomography.
  Cell Motil Cytoskeleton, 62, 69-83.  
15653077 R.McIntosh, D.Nicastro, and D.Mastronarde (2005).
New views of cells in 3D: an introduction to electron tomography.
  Trends Cell Biol, 15, 43-51.  
15952904 V.Lucić, F.Förster, and W.Baumeister (2005).
Structural studies by electron tomography: from cells to molecules.
  Annu Rev Biochem, 74, 833-865.  
15318169 A.Al-Amoudi, J.J.Chang, A.Leforestier, A.McDowall, L.M.Salamin, L.P.Norlén, K.Richter, N.S.Blanc, D.Studer, and J.Dubochet (2004).
Cryo-electron microscopy of vitreous sections.
  EMBO J, 23, 3583-3588.  
15130472 A.W.Koch, A.Farooq, W.Shan, L.Zeng, D.R.Colman, and M.M.Zhou (2004).
Structure of the neural (N-) cadherin prodomain reveals a cadherin extracellular domain-like fold without adhesive characteristics.
  Structure, 12, 793-805.
PDB code: 1op4
15304105 C.Moss, A.Martinez-Mir, H.Lam, M.Tadin-Strapps, A.Kljuic, and A.M.Christiano (2004).
A recurrent intragenic deletion in the desmoglein 4 gene underlies localized autosomal recessive hypotrichosis.
  J Invest Dermatol, 123, 607-610.  
15071499 D.Häussinger, T.Ahrens, T.Aberle, J.Engel, J.Stetefeld, and S.Grzesiek (2004).
Proteolytic E-cadherin activation followed by solution NMR and X-ray crystallography.
  EMBO J, 23, 1699-1708.
PDB code: 1q1p
15546992 E.Perret, A.Leung, H.Feracci, and E.Evans (2004).
Trans-bonded pairs of E-cadherin exhibit a remarkable hierarchy of mechanical strengths.
  Proc Natl Acad Sci U S A, 101, 16472-16477.  
15112230 J.M.Gooding, K.L.Yap, and M.Ikura (2004).
The cadherin-catenin complex as a focal point of cell adhesion and signalling: new insights from three-dimensional structures.
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15609097 M.Goodwin, and A.S.Yap (2004).
Classical cadherin adhesion molecules: coordinating cell adhesion, signaling and the cytoskeleton.
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15464893 R.D.Leapman (2004).
Novel techniques in electron microscopy.
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15071552 S.Getsios, A.C.Huen, and K.J.Green (2004).
Working out the strength and flexibility of desmosomes.
  Nat Rev Mol Cell Biol, 5, 271-281.  
15606501 S.Getsios, E.V.Amargo, R.L.Dusek, K.Ishii, L.Sheu, L.M.Godsel, and K.J.Green (2004).
Coordinated expression of desmoglein 1 and desmocollin 1 regulates intercellular adhesion.
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15561586 T.Yin, and K.J.Green (2004).
Regulation of desmosome assembly and adhesion.
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  14964308 U.Cavallaro, and G.Christofori (2004).
Cell adhesion and signalling by cadherins and Ig-CAMs in cancer.
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14675546 S.D.Patel, C.P.Chen, F.Bahna, B.Honig, and L.Shapiro (2003).
Cadherin-mediated cell-cell adhesion: sticking together as a family.
  Curr Opin Struct Biol, 13, 690-698.  
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 codes are shown on the right.