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Growth factor PDB id
1tgj
Jmol
Contents
Protein chain
112 a.a. *
Ligands
DIO
Waters ×77
* Residue conservation analysis
PDB id:
1tgj
Name: Growth factor
Title: Human transforming growth factor-beta 3, crystallized from d
Structure: Transforming growth factor-beta 3. Chain: a. Synonym: tgf-beta3. Engineered: yes. Other_details: one dioxane molecule bound
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: htgf-beta3. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: strain deposited at deutsche sammlung von mikroorganismen, maschenroder weg 1b, 3300 braunschweig, ge accession number is dsm 5658
Biol. unit: Dimer (from PDB file)
Resolution:
2.00Å     R-factor:   0.175    
Authors: P.R.E.Mittl,J.P.Priestle,M.G.Gruetter
Key ref:
P.R.Mittl et al. (1996). The crystal structure of TGF-beta 3 and comparison to TGF-beta 2: implications for receptor binding. Protein Sci, 5, 1261-1271. PubMed id: 8819159 Ref: Full text
Date:
09-Jul-96     Release date:   11-Jan-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P10600  (TGFB3_HUMAN) -  Transforming growth factor beta-3
Seq:
Struc: 		412 a.a.
112 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     cell growth   1 term 
  Biochemical function     growth factor activity     2 terms  

 

 
Full text Protein Sci 5:1261-1271 (1996)
PubMed id: 8819159  
 
 
The crystal structure of TGF-beta 3 and comparison to TGF-beta 2: implications for receptor binding.
P.R.Mittl, J.P.Priestle, D.A.Cox, G.McMaster, N.Cerletti, M.G.Grütter.
 
  ABSTRACT  
 
Transforming growth factors beta belong to a group of cytokines that control cellular proliferation and differentiation. Five isoforms are known that share approximately 75% sequence identity, but exert different biological activities. The structure of TGF-beta 3 was solved by X-ray crystallography and refined to a final R-factor of 17.5% at 2.0 A resolution. Comparison with the structure of TGF-beta 2 (Schlunegger MP, Grütter MG, 1992, Nature 358:430-434; Daopin S, Piez KA, Ogawa Y, Davies DR, 1992, Science 257:369-373) reveals a virtually identical central core. Differences exist in the conformations of the N-terminal alpha-helix and in the beta-sheet loops. In TGF-beta 3, the N-terminal alpha-helix has moved approximately 1 A away from the central core. This movement can be correlated with the mutation of Leu 17 to Val and Ala 47 to Pro in TGF-beta 3. The beta-sheet loops rotate as a rigid body 9 degrees around an axis that runs approximately parallel to the dimer axis. If these differences are recognized by the TGF-beta receptors, they might account for the individual cellular responses. A molecule of the precipitating agent dioxane is bound in a crystal contact, forming a hydrogen bond with Trp 32. This dioxane may occupy a carbohydrate-binding site, because dioxane possesses some structural similarity with a carbohydrate. The dioxane is in contact with two tryptophans, which are often involved in carbohydrate recognition.
 
  Selected figure(s)  
 
Figure 6.
Fig. 6. Superposition of TGF-03 and TGF-82, ased on the residuesfromthecenralcore(residues15-22, 41-84, 103-112, 15#-22#, 41#-84#, 103#-112#) andviewedparallel to he dimer axis. For clarity, only the entralcore TGF-03 is shown. ifferent conformations arefoundfortheN-terminal a-helix residues1-14)andthe 8-sheets loops residues23-40and 85-102), whichare shown nred for TGF-03 andingreen for TGF-02. 		Figure 9.
Fig. 9. Bindingsite f thedioxanethat s buriedinacrystalcontact.Themainchainsareindicated by tubesinlightanddark grey forthetwoindependentsubunits.Residuesthatcontactthedioxane in theTGF-03(tri)structureareshownasball-and- stickmodels(drawnusingMOLSCRIPT,Kraulis[1991]).IntheTGF-P3(hex)structure,thesidechain of Trp 2hasrotated 150'' around x2, hich is showninthinlines.
 
  The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (1996, 5, 1261-1271) copyright 1996.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20161792 C.S.Starck, and A.J.Sutherland-Smith (2010).
Cytotoxic aggregation and amyloid formation by the myostatin precursor protein.
  PLoS One, 5, e9170.  
20890540 L.Li, B.P.Orner, T.Huang, A.P.Hinck, and L.L.Kiessling (2010).
Peptide ligands that use a novel binding site to target both TGF-β receptors.
  Mol Biosyst, 6, 2392-2402.  
19656717 H.G.Laverty, L.M.Wakefield, N.L.Occleston, S.O'Kane, and M.W.Ferguson (2009).
TGF-beta3 and cancer: a review.
  Cytokine Growth Factor Rev, 20, 305-317.  
19161338 J.Baardsnes, C.S.Hinck, A.P.Hinck, and M.D.O'Connor-McCourt (2009).
TbetaR-II discriminates the high- and low-affinity TGF-beta isoforms via two hydrogen-bonded ion pairs.
  Biochemistry, 48, 2146-2155.  
19073914 C.Grütter, T.Wilkinson, R.Turner, S.Podichetty, D.Finch, M.McCourt, S.Loning, L.Jermutus, and M.G.Grütter (2008).
A cytokine-neutralizing antibody as a structural mimetic of 2 receptor interactions.
  Proc Natl Acad Sci U S A, 105, 20251-20256.
PDB codes: 3eo0 3eo1
18243111 J.Groppe, C.S.Hinck, P.Samavarchi-Tehrani, C.Zubieta, J.P.Schuermann, A.B.Taylor, P.M.Schwarz, J.L.Wrana, and A.P.Hinck (2008).
Cooperative assembly of TGF-beta superfamily signaling complexes is mediated by two disparate mechanisms and distinct modes of receptor binding.
  Mol Cell, 29, 157-168.
PDB code: 2pjy
18331637 K.Manikandan, D.Pal, S.Ramakumar, N.E.Brener, S.S.Iyengar, and G.Seetharaman (2008).
Functionally important segments in proteins dissected using Gene Ontology and geometric clustering of peptide fragments.
  Genome Biol, 9, R52.  
17146441 T.Shimanuki, T.Hara, T.Furuya, T.Imamura, and K.Miyazono (2007).
Modulation of the functional binding sites for TGF-beta on the type II receptor leads to suppression of TGF-beta signaling.
  Oncogene, 26, 3311-3320.  
17525753 Y.P.Rubtsov, and A.Y.Rudensky (2007).
TGFbeta signalling in control of T-cell-mediated self-reactivity.
  Nat Rev Immunol, 7, 443-453.  
16795047 O.Maissen, C.Eckhardt, S.Gogolewski, M.Glatt, T.Arvinte, A.Steiner, B.Rahn, and U.Schlegel (2006).
Mechanical and radiological assessment of the influence of rhTGFbeta-3 on bone regeneration in a segmental defect in the ovine tibia: pilot study.
  J Orthop Res, 24, 1670-1678.  
  16508114 T.D.Mueller, M.Gottermeier, W.Sebald, and J.Nickel (2005).
Crystallization and preliminary X-ray diffraction analysis of human growth and differentiation factor 5 (GDF-5).
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 134-136.  
14627550 J.P.Hanrahan, S.M.Gregan, P.Mulsant, M.Mullen, G.H.Davis, R.Powell, and S.M.Galloway (2004).
Mutations in the genes for oocyte-derived growth factors GDF9 and BMP15 are associated with both increased ovulation rate and sterility in Cambridge and Belclare sheep (Ovis aries).
  Biol Reprod, 70, 900-909.  
  14746809 M.de Caestecker (2004).
The transforming growth factor-beta superfamily of receptors.
  Cytokine Growth Factor Rev, 15, 1.  
15473835 S.J.Lee (2004).
Regulation of muscle mass by myostatin.
  Annu Rev Cell Dev Biol, 20, 61-86.  
15449706 W.Sebald, J.Nickel, J.L.Zhang, and T.D.Mueller (2004).
Molecular recognition in bone morphogenetic protein (BMP)/receptor interaction.
  Biol Chem, 385, 697-710.  
  15931280 K.C.Flanders, and J.K.Burmester (2003).
Medical applications of transforming growth factor-beta.
  Clin Med Res, 1, 13-20.  
12660162 T.B.Thompson, T.K.Woodruff, and T.S.Jardetzky (2003).
Structures of an ActRIIB:activin A complex reveal a novel binding mode for TGF-beta ligand:receptor interactions.
  EMBO J, 22, 1555-1566.
PDB codes: 1nys 1nyu
12809600 Y.Shi, and J.Massagué (2003).
Mechanisms of TGF-beta signaling from cell membrane to the nucleus.
  Cell, 113, 685-700.  
  11772446 A.Jen, K.Madörin, K.Vosbeck, T.Arvinte, and H.P.Merkle (2002).
Transforming growth factor beta-3 crystals as reservoirs for slow release of active TGF-beta3.
  J Control Release, 78, 25-34.  
  12121646 C.C.Boesen, S.Radaev, S.A.Motyka, A.Patamawenu, and P.D.Sun (2002).
The 1.1 A crystal structure of human TGF-beta type II receptor ligand binding domain.
  Structure, 10, 913-919.
PDB code: 1m9z
11850637 P.J.Hart, S.Deep, A.B.Taylor, Z.Shu, C.S.Hinck, and A.P.Hinck (2002).
Crystal structure of the human TbetaR2 ectodomain--TGF-beta3 complex.
  Nat Struct Biol, 9, 203-208.
PDB code: 1ktz
  11707292 J.Yue, and K.M.Mulder (2001).
Transforming growth factor-beta signal transduction in epithelial cells.
  Pharmacol Ther, 91, 1.  
11141057 W.D.Fairlie, P.K.Russell, W.M.Wu, A.G.Moore, H.P.Zhang, P.K.Brown, A.R.Bauskin, and S.N.Breit (2001).
Epitope mapping of the transforming growth factor-beta superfamily protein, macrophage inhibitory cytokine-1 (MIC-1): identification of at least five distinct epitope specificities.
  Biochemistry, 40, 65-73.  
10716989 P.R.Mittl, C.Deillon, D.Sargent, N.Liu, S.Klauser, R.M.Thomas, B.Gutte, and M.G.Grütter (2000).
The retro-GCN4 leucine zipper sequence forms a stable three-dimensional structure.
  Proc Natl Acad Sci U S A, 97, 2562-2566.
PDB code: 1c94
10880444 T.Kirsch, J.Nickel, and W.Sebald (2000).
BMP-2 antagonists emerge from alterations in the low-affinity binding epitope for receptor BMPR-II.
  EMBO J, 19, 3314-3324.  
  9165082 A.Bergner, T.Muta, S.Iwanaga, H.G.Beisel, R.Delotto, and W.Bode (1997).
Horseshoe crab coagulogen is an invertebrate protein with a nerve growth factor-like domain.
  Biol Chem, 378, 283-287.  
9356471 A.C.McPherron, and S.J.Lee (1997).
Double muscling in cattle due to mutations in the myostatin gene.
  Proc Natl Acad Sci U S A, 94, 12457-12461.  
  9351807 Y.A.Muller, H.W.Christinger, B.A.Keyt, and A.M.de Vos (1997).
The crystal structure of vascular endothelial growth factor (VEGF) refined to 1.93 A resolution: multiple copy flexibility and receptor binding.
  Structure, 5, 1325-1338.
PDB code: 2vpf
  9003754 A.Bergner, V.Oganessyan, T.Muta, S.Iwanaga, D.Typke, R.Huber, and W.Bode (1996).
Crystal structure of a coagulogen, the clotting protein from horseshoe crab: a structural homologue of nerve growth factor.
  EMBO J, 15, 6789-6797.
PDB code: 1aoc
8917430 J.F.Goetschy, O.Letourneur, N.Cerletti, and M.A.Horisberger (1996).
The unglycosylated extracellular domain of type-II receptor for transforming growth factor-beta. A novel assay for characterizing ligand affinity and specificity.
  Eur J Biochem, 241, 355-362.  
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.