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PDBsum entry 1yo8

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protein ligands metals links
Cell adhesion PDB id
1yo8
Jmol
Contents
Protein chain
621 a.a. *
Ligands
NAG-NAG-MAN
NAG-NAG
NAG ×2
Metals
_CA ×30
Waters ×116
* Residue conservation analysis
PDB id:
1yo8
Name: Cell adhesion
Title: Structure of thE C-terminal domain of human thrombospondin-2
Structure: Thrombospondin-2. Chain: a. Fragment: c-terminal domain. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: thbs2, tsp2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Resolution:
2.60Å     R-factor:   0.224     R-free:   0.284
Authors: C.B.Carlson,D.A.Bernstein,D.S.Annis,T.M.Misenheimer,B.A.Hann D.F.Mosher,J.L.Keck
Key ref:
C.B.Carlson et al. (2005). Structure of the calcium-rich signature domain of human thrombospondin-2. Nat Struct Mol Biol, 12, 910-914. PubMed id: 16186819 DOI: 10.1038/nsmb997
Date:
26-Jan-05     Release date:   27-Sep-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P35442  (TSP2_HUMAN) -  Thrombospondin-2
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1172 a.a.
621 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   2 terms 
  Biological process     cell adhesion   2 terms 
  Biochemical function     calcium ion binding     2 terms  

 

 
DOI no: 10.1038/nsmb997 Nat Struct Mol Biol 12:910-914 (2005)
PubMed id: 16186819  
 
 
Structure of the calcium-rich signature domain of human thrombospondin-2.
C.B.Carlson, D.A.Bernstein, D.S.Annis, T.M.Misenheimer, B.L.Hannah, D.F.Mosher, J.L.Keck.
 
  ABSTRACT  
 
Thrombospondins (THBSs) are secreted glycoproteins that have key roles in interactions between cells and the extracellular matrix. Here, we describe the 2.6-A-resolution crystal structure of the glycosylated signature domain of human THBS2, which includes three epidermal growth factor-like modules, 13 aspartate-rich repeats and a lectin-like module. These elements interact extensively to form three structural regions termed the stalk, wire and globe. The THBS2 signature domain is stabilized by these interactions and by a network of 30 bound Ca(2+) ions and 18 disulfide bonds. The structure suggests how genetic alterations of THBSs result in disease.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Structure of human THBS2. (a) Schematic diagram of THBS2. Each THBS2 monomer is composed of a N-terminal module (N), an oligomerization domain (O), a procollagen module (C) and type 1 or properdin modules (P1, P2 and P3) followed by the signature domain common to all THBSs. Yellow, EGF1 (residues 551 -589); orange, EGF2 (590 -647); beige, EGF3 (648 -692); blue, aspartate-rich repeats (693 -956); magenta, lectin-like module (957 -1172); green ovals, glycosylation sites; arrowhead above EGF-like repeats, the position of an extra EGF-like module in THBS3, THBS4 and THBS5. (b) Stereo diagram of the glycosylated residue Asn1069. The 2F[o] - F[c] electron-density map for the region is shown, contoured at 1.3 . (c) Four views of the crystal structure of the signature domain of human THBS2. Module coloration is as in a; red spheres, Ca^2+ ions; green, carbohydrates. Disulfide bonds (stick representation) are shown.
Figure 2.
Figure 2. Ca^2+ coordination in the stalk and wire elements of THBS2. Coloring is as in Figure 1. (a) Ca^2+ coordination at the interface between EGF1 and EGF2. Ca^2+-coordinating residues are shown and labeled. mc, residues that coordinate Ca^2+ via main chain carbonyl groups. (b) Overlay of the five N-type Ca^2+-binding motifs. Ca^2+-binding residues are labeled. Xxx, any residue; red atoms, oxygen. (c) Overlay of the eight C-type Ca^2+-binding motifs. The insert sequence from repeat 1C has been removed for the alignment. (d) The glycosylated insertion element in repeat 1C and coordination of an additional Ca^2+ between repeats 2N and 3C, highlighted by showing 1C, 2N, 3C and 4C in stereo. (e) Alignment of Ca^2+-binding repeats in the wire. Red residues, side chains bind two Ca^2+; purple, side chains bind one Ca^2+; green or underlined, main chain carbonyls bind one Ca^2+; blue or italic, water-mediated Ca^2+ binding; red lines, disulfide bonds; + and -, N-type repeats that bind three or one Ca^2+, respectively, rather than two; arrowhead above repeat 1C, site of the 13-residue insertion, whose sequence is shown above; arrowhead above repeat 11C, site of the 4-residue insertion in THBS3 and THBS4. Residue numbers are listed at left and coordination numbering shown above.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2005, 12, 910-914) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20427418 A.A.Bentley, and J.C.Adams (2010).
The evolution of thrombospondins and their ligand-binding activities.
  Mol Biol Evol, 27, 2187-2197.  
20056600 G.Colombo, B.Margosio, L.Ragona, M.Neves, S.Bonifacio, D.S.Annis, M.Stravalaci, S.Tomaselli, R.Giavazzi, M.Rusnati, M.Presta, L.Zetta, D.F.Mosher, D.Ribatti, M.Gobbi, and G.Taraboletti (2010).
Non-peptidic thrombospondin-1 mimics as fibroblast growth factor-2 inhibitors: an integrated strategy for the development of new antiangiogenic compounds.
  J Biol Chem, 285, 8733-8742.  
20508815 K.A.Piróg, and M.D.Briggs (2010).
Skeletal dysplasias associated with mild myopathy-a clinical and molecular review.
  J Biomed Biotechnol, 2010, 686457.  
19262692 A.Kranjc, F.W.Grillo, J.Rievaj, A.Boccaccio, F.Pietrucci, A.Menini, P.Carloni, and C.Anselmi (2009).
Regulation of bestrophins by Ca2+: a theoretical and experimental study.
  PLoS ONE, 4, e4672.  
18952113 A.Liu, D.F.Mosher, J.E.Murphy-Ullrich, and S.E.Goldblum (2009).
The counteradhesive proteins, thrombospondin 1 and SPARC/osteonectin, open the tyrosine phosphorylation-responsive paracellular pathway in pulmonary vascular endothelia.
  Microvasc Res, 77, 13-20.  
19129184 A.Liu, P.Garg, S.Yang, P.Gong, M.A.Pallero, D.S.Annis, Y.Liu, A.Passaniti, D.Mann, D.F.Mosher, J.E.Murphy-Ullrich, and S.E.Goldblum (2009).
Epidermal Growth Factor-like Repeats of Thrombospondins Activate Phospholipase C{gamma} and Increase Epithelial Cell Migration through Indirect Epidermal Growth Factor Receptor Activation.
  J Biol Chem, 284, 6389-6402.  
19830595 K.Tan, and J.Lawler (2009).
The interaction of Thrombospondins with extracellular matrix proteins.
  J Cell Commun Signal, 3, 177-187.  
19276170 K.Tan, M.Duquette, A.Joachimiak, and J.Lawler (2009).
The crystal structure of the signature domain of cartilage oligomeric matrix protein: implications for collagen, glycosaminoglycan and integrin binding.
  FASEB J, 23, 2490-2501.
PDB code: 3fby
19706610 Y.Liu, and D.F.Mosher (2009).
Interactions among stalk modules of thrombospondin-1.
  J Biol Chem, 284, 28563-28570.  
19531495 Y.Liu, D.S.Annis, and D.F.Mosher (2009).
Interactions among the epidermal growth factor-like modules of thrombospondin-1.
  J Biol Chem, 284, 22206-22212.  
17996481 B.Margosio, M.Rusnati, K.Bonezzi, B.L.Cordes, D.S.Annis, C.Urbinati, R.Giavazzi, M.Presta, D.Ribatti, D.F.Mosher, and G.Taraboletti (2008).
Fibroblast growth factor-2 binding to the thrombospondin-1 type III repeats, a novel antiangiogenic domain.
  Int J Biochem Cell Biol, 40, 700-709.  
18193164 C.B.Carlson, J.Lawler, and D.F.Mosher (2008).
Structures of thrombospondins.
  Cell Mol Life Sci, 65, 672-686.  
18682400 C.B.Carlson, K.A.Gunderson, and D.F.Mosher (2008).
Mutations targeting intermodular interfaces or calcium binding destabilize the thrombospondin-2 signature domain.
  J Biol Chem, 283, 27089-27099.  
18499674 C.B.Carlson, Y.Liu, J.L.Keck, and D.F.Mosher (2008).
Influences of the N700S thrombospondin-1 polymorphism on protein structure and stability.
  J Biol Chem, 283, 20069-20076.
PDB code: 2rhp
18226512 M.J.Calzada, S.A.Kuznetsova, J.M.Sipes, R.G.Rodrigues, J.A.Cashel, D.S.Annis, D.F.Mosher, and D.D.Roberts (2008).
Calcium indirectly regulates immunochemical reactivity and functional activities of the N-domain of thrombospondin-1.
  Matrix Biol, 27, 339-351.  
17570134 T.L.Chen, K.L.Posey, J.T.Hecht, and B.M.Vertel (2008).
COMP mutations: Domain-dependent relationship between abnormal chondrocyte trafficking and clinical PSACH and MED phenotypes.
  J Cell Biochem, 103, 778-787.  
17620335 D.S.Annis, K.A.Gunderson, and D.F.Mosher (2007).
Immunochemical analysis of the structure of the signature domains of thrombospondin-1 and thrombospondin-2 in low calcium concentrations.
  J Biol Chem, 282, 27067-27075.  
17588949 F.H.Chen, M.E.Herndon, N.Patel, J.T.Hecht, R.S.Tuan, and J.Lawler (2007).
Interaction of cartilage oligomeric matrix protein/thrombospondin 5 with aggrecan.
  J Biol Chem, 282, 24591-24598.  
17588960 K.A.Piróg-Garcia, R.S.Meadows, L.Knowles, D.Heinegård, D.J.Thornton, K.E.Kadler, R.P.Boot-Handford, and M.D.Briggs (2007).
Reduced cell proliferation and increased apoptosis are significant pathological mechanisms in a murine model of mild pseudoachondroplasia resulting from a mutation in the C-terminal domain of COMP.
  Hum Mol Genet, 16, 2072-2088.  
17559888 X.Zhang, and J.Lawler (2007).
Thrombospondin-based antiangiogenic therapy.
  Microvasc Res, 74, 90-99.  
16420580 D.S.Annis, J.E.Murphy-Ullrich, and D.F.Mosher (2006).
Function-blocking antithrombospondin-1 monoclonal antibodies.
  J Thromb Haemost, 4, 459-468.  
16684956 J.I.Zwicker, F.Peyvandi, R.Palla, R.Lombardi, M.T.Canciani, A.Cairo, D.Ardissino, L.Bernardinelli, K.A.Bauer, J.Lawler, and P.Mannucci (2006).
The thrombospondin-1 N700S polymorphism is associated with early myocardial infarction without altering von Willebrand factor multimer size.
  Blood, 108, 1280-1283.  
16835222 J.S.Isenberg, L.A.Ridnour, J.Dimitry, W.A.Frazier, D.A.Wink, and D.D.Roberts (2006).
CD47 is necessary for inhibition of nitric oxide-stimulated vascular cell responses by thrombospondin-1.
  J Biol Chem, 281, 26069-26080.  
16928687 M.Schmitz, A.Becker, A.Schmitz, C.Weirich, M.Paulsson, F.Zaucke, and R.Dinser (2006).
Disruption of extracellular matrix structure may cause pseudoachondroplasia phenotypes in the absence of impaired cartilage oligomeric matrix protein secretion.
  J Biol Chem, 281, 32587-32595.  
16620379 P.McKenzie, S.C.Chadalavada, J.Bohrer, and J.C.Adams (2006).
Phylogenomic analysis of vertebrate thrombospondins reveals fish-specific paralogues, ancestral gene relationships and a tetrapod innovation.
  BMC Evol Biol, 6, 33.  
16246837 T.M.Misenheimer, and D.F.Mosher (2005).
Biophysical characterization of the signature domains of thrombospondin-4 and thrombospondin-2.
  J Biol Chem, 280, 41229-41235.  
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.