PDBsum entry 1uzj

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protein metals Protein-protein interface(s) links
Matrix protein PDB id
Protein chains
162 a.a. *
_CA ×6
Waters ×215
* Residue conservation analysis
PDB id:
Name: Matrix protein
Title: Integrin binding cbegf22-tb4-cbegf33 fragment of human fibrillin-1, holo form.
Structure: Fibrillin-1. Chain: a, b, c. Fragment: begf22-tb4-cbegf23, residues 1486-1647. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Tissue: extra-ellular matrix. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.25Å     R-factor:   0.247     R-free:   0.318
Authors: S.S.J.Lee,V.Knott,K.Harlos,P.A.Handford,D.I.Stuart
Key ref:
S.S.Lee et al. (2004). Structure of the integrin binding fragment from fibrillin-1 gives new insights into microfibril organization. Structure, 12, 717-729. PubMed id: 15062093 DOI: 10.1016/j.str.2004.02.023
12-Mar-04     Release date:   08-Apr-04    
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Protein chains
Pfam   ArchSchema ?
P35555  (FBN1_HUMAN) -  Fibrillin-1
2871 a.a.
162 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     proteinaceous extracellular matrix   1 term 
  Biochemical function     extracellular matrix structural constituent     2 terms  


DOI no: 10.1016/j.str.2004.02.023 Structure 12:717-729 (2004)
PubMed id: 15062093  
Structure of the integrin binding fragment from fibrillin-1 gives new insights into microfibril organization.
S.S.Lee, V.Knott, J.Jovanović, K.Harlos, J.M.Grimes, L.Choulier, H.J.Mardon, D.I.Stuart, P.A.Handford.
Human fibrillin-1, the major structural protein of extracellular matrix (ECM) 10-12 nm microfibrils, is dominated by 43 calcium binding epidermal growth factor-like (cbEGF) and 7 transforming growth factor beta binding protein-like (TB) domains. Crystal structures reveal the integrin binding cbEGF22-TB4-cbEGF23 fragment of human fibrillin-1 to be a Ca(2+)-rigidified tetragonal pyramid. We suggest that other cbEGF-TB pairs within the fibrillins may adopt a similar orientation to cbEGF22-TB4. In addition, we have located a flexible RGD integrin binding loop within TB4. Modeling, cell attachment and spreading assays, immunocytochemistry, and surface plasmon resonance indicate that cbEGF22 bound to TB4 is a requirement for integrin activation and provide insight into the molecular basis of the fibrillin-1 interaction with alphaVbeta3. In light of our data, we propose a novel model for the assembly of the fibrillin microfibril and a mechanism to explain its extensibility.
  Selected figure(s)  
Figure 6.
Figure 6. Models of Fibrillin-1 and Microfibril Organization(A) Homology model for cbEGF11-TB5. cbEGF and TB domains are colored green and blue, respectively. The crystal structure of cbEGF22-TB4-cbEGF23 fragment is highlighted in bold. Ca^2+ and potential N-linked glycosylation sites are represented by red and black spheres, respectively. The RGD motif on the TB4 loop is indicated.(B) A simple model of the fibrillin microfibril. The arrows represent fibrillin-1 molecules with dimensions based on the knowledge of the component domains. The intermolecular transglutaminase cross-links are shown as X and the associated protein MAGP-1 as a turquoise diamond. A sketch of the STEM data of Baldock et al. (2001) is shown below. The colored regions mark the sites of known antibody epitopes (red, 2502; green, 11C1.3; purple, PF2; yellow, 2499). The bead regions are shown as gray ellipses.
  The above figure is reprinted by permission from Cell Press: Structure (2004, 12, 717-729) copyright 2004.  
  Figure was selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19513754 F.Ramirez, and L.Y.Sakai (2010).
Biogenesis and function of fibrillin assemblies.
  Cell Tissue Res, 339, 71-82.  
21175431 I.Robertson, S.Jensen, and P.Handford (2010).
TB domain proteins: evolutionary insights into the multifaceted roles of fibrillins and LTBPs.
  Biochem J, 433, 263-276.  
19446519 D.Hubmacher, and D.P.Reinhardt (2009).
One more piece in the fibrillin puzzle.
  Structure, 17, 635-636.  
19884902 I.El-Hamamsy, and M.H.Yacoub (2009).
Cellular and molecular mechanisms of thoracic aortic aneurysms.
  Nat Rev Cardiol, 6, 771-786.  
19037100 L.Sabatier, D.Chen, C.Fagotto-Kaufmann, D.Hubmacher, M.D.McKee, D.S.Annis, D.F.Mosher, and D.P.Reinhardt (2009).
Fibrillin assembly requires fibronectin.
  Mol Biol Cell, 20, 846-858.  
19588272 M.J.Sherratt (2009).
Tissue elasticity and the ageing elastic fibre.
  Age (Dordr), 31, 305-325.  
19446531 S.A.Jensen, S.Iqbal, E.D.Lowe, C.Redfield, and P.A.Handford (2009).
Structure and interdomain interactions of a hybrid domain: a disulphide-rich module of the fibrillin/LTBP superfamily of matrix proteins.
  Structure, 17, 759-768.
PDB code: 2w86
17158461 C.L.Kuo, Z.Isogai, D.R.Keene, N.Hazeki, R.N.Ono, G.Sengle, H.Peter Bächinger, and L.Y.Sakai (2007).
Effects of fibrillin-1 degradation on microfibril ultrastructure.
  J Biol Chem, 282, 4007-4020.  
17588872 C.M.Kielty, S.Stephan, M.J.Sherratt, M.Williamson, and C.A.Shuttleworth (2007).
Applying elastic fibre biology in vascular tissue engineering.
  Philos Trans R Soc Lond B Biol Sci, 362, 1293-1312.  
17033827 D.Egging, F.van den Berkmortel, G.Taylor, J.Bristow, and J.Schalkwijk (2007).
Interactions of human tenascin-X domains with dermal extracellular matrix molecules.
  Arch Dermatol Res, 298, 389-396.  
17708531 F.Ramirez, and H.C.Dietz (2007).
Fibrillin-rich microfibrils: Structural determinants of morphogenetic and homeostatic events.
  J Cell Physiol, 213, 326-330.  
17942296 I.Vakonakis, and I.D.Campbell (2007).
Extracellular matrix: from atomic resolution to ultrastructure.
  Curr Opin Cell Biol, 19, 578-583.  
17158881 J.Jovanovic, J.Takagi, L.Choulier, N.G.Abrescia, D.I.Stuart, P.A.van der Merwe, H.J.Mardon, and P.A.Handford (2007).
alphaVbeta6 is a novel receptor for human fibrillin-1. Comparative studies of molecular determinants underlying integrin-rgd affinity and specificity.
  J Biol Chem, 282, 6743-6751.  
17942298 J.Takagi (2007).
Structural basis for ligand recognition by integrins.
  Curr Opin Cell Biol, 19, 557-564.  
16905551 K.T.Mellody, L.J.Freeman, C.Baldock, T.A.Jowitt, V.Siegler, B.D.Raynal, S.A.Cain, T.J.Wess, C.A.Shuttleworth, and C.M.Kielty (2006).
Marfan syndrome-causing mutations in fibrillin-1 result in gross morphological alterations and highlight the structural importance of the second hybrid domain.
  J Biol Chem, 281, 31854-31862.  
16571647 P.N.Robinson, E.Arteaga-Solis, C.Baldock, G.Collod-Béroud, P.Booms, A.De Paepe, H.C.Dietz, G.Guo, P.A.Handford, D.P.Judge, C.M.Kielty, B.Loeys, D.M.Milewicz, A.Ney, F.Ramirez, D.P.Reinhardt, K.Tiedemann, P.Whiteman, and M.Godfrey (2006).
The molecular genetics of Marfan syndrome and related disorders.
  J Med Genet, 43, 769-787.  
16677079 P.Whiteman, S.Hutchinson, and P.A.Handford (2006).
Fibrillin-1 misfolding and disease.
  Antioxid Redox Signal, 8, 338-346.  
17005021 S.Stephan, S.G.Ball, M.Williamson, D.V.Bax, A.Lomas, C.A.Shuttleworth, and C.M.Kielty (2006).
Cell-matrix biology in vascular tissue engineering.
  J Anat, 209, 495-502.  
15611103 D.B.Rifkin (2005).
Latent transforming growth factor-beta (TGF-beta) binding proteins: orchestrators of TGF-beta availability.
  J Biol Chem, 280, 7409-7412.  
16096271 D.Hubmacher, K.Tiedemann, R.Bartels, J.Brinckmann, T.Vollbrandt, B.Bätge, H.Notbohm, and D.P.Reinhardt (2005).
Modification of the structure and function of fibrillin-1 by homocysteine suggests a potential pathogenetic mechanism in homocystinuria.
  J Biol Chem, 280, 34946-34955.  
16252250 R.L.Rich, and D.G.Myszka (2005).
Survey of the year 2004 commercial optical biosensor literature.
  J Mol Recognit, 18, 431-478.  
15980072 S.A.Cain, C.Baldock, J.Gallagher, A.Morgan, D.V.Bax, A.S.Weiss, C.A.Shuttleworth, and C.M.Kielty (2005).
Fibrillin-1 interactions with heparin. Implications for microfibril and elastic fiber assembly.
  J Biol Chem, 280, 30526-30537.  
15649891 S.A.Jensen, A.R.Corbett, V.Knott, C.Redfield, and P.A.Handford (2005).
Ca2+-dependent interface formation in fibrillin-1.
  J Biol Chem, 280, 14076-14084.  
15130465 M.A.Arnaout (2004).
The structural basis of elasticity in fibrillin-based microfibrils.
  Structure, 12, 734-736.  
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.