PDBsum entry 1hwh

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protein Protein-protein interface(s) links
Complex (hormone/receptor) PDB id
Protein chains
185 a.a. *
196 a.a. *
* Residue conservation analysis
PDB id:
Name: Complex (hormone/receptor)
Title: 1:1 complex of human growth hormone mutant g120r with its soluble binding protein
Structure: Growth hormone. Chain: a. Engineered: yes. Mutation: yes. Growth hormone binding protein. Chain: b. Fragment: extracellular domain. Engineered: yes. Other_details: one hormone with one receptor molecule
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562
Biol. unit: Homo-Dimer (from PDB file)
2.90Å     R-factor:   0.215     R-free:   0.317
Authors: S.M.Sundstrom,T.Lundqvist
Key ref:
M.Sundström et al. (1996). Crystal structure of an antagonist mutant of human growth hormone, G120R, in complex with its receptor at 2.9 A resolution. J Biol Chem, 271, 32197-32203. PubMed id: 8943276 DOI: 10.1074/jbc.271.50.32197
13-Nov-96     Release date:   19-Nov-97    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P01241  (SOMA_HUMAN) -  Somatotropin
217 a.a.
185 a.a.*
Protein chain
Pfam   ArchSchema ?
P10912  (GHR_HUMAN) -  Growth hormone receptor
638 a.a.
196 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   3 terms 
  Biological process     bone maturation   16 terms 
  Biochemical function     protein binding     7 terms  


DOI no: 10.1074/jbc.271.50.32197 J Biol Chem 271:32197-32203 (1996)
PubMed id: 8943276  
Crystal structure of an antagonist mutant of human growth hormone, G120R, in complex with its receptor at 2.9 A resolution.
M.Sundström, T.Lundqvist, J.Rödin, L.B.Giebel, D.Milligan, G.Norstedt.
Human growth hormone binds two receptor molecules and thereby induces signal transduction through receptor dimerization. At high concentrations, growth hormone acts as an antagonist because of a large difference in affinities at the respective binding sites. This antagonist action can be enhanced further by reducing binding in the low affinity binding site. A growth hormone antagonist mutant Gly-120 --> Arg, has been crystallized with its receptor as a 1:1 complex and the crystal structure determined at 2.9 A resolution. The 1:1 complex is remarkably similar to the native growth hormone-receptor 1:2 complex. A comparison between the two structures reveals only minimal differences in the conformations of the hormone or its receptor in the two complexes, including the angle between the two immunoglobulin-like domains of the receptor. Further, two symmetry-related 1:1 complexes in the crystal form a 2:2 complex with a large solvent inaccessible area between two receptor molecules. In addition, we present here a native human growth hormone-human growth hormone-binding protein 1:2 complex structure at 2.5 A resolution. One important difference between our structure and the previously published crystal structure at 2.8 A is revealed. Trp-104 in the receptor, a key residue in the hormone-receptor interaction, has an altered conformation in the low affinity site enabling a favorable hydrogen bond to be formed with Asp-116 of the hormone.
  Selected figure(s)  
Figure 1.
Fig. 1. Schematic representation of the general architecture of the 1:2 complex. The two receptor molecules are in red (high affinity) and yellow (low affinity). The picture was generated^ using MOLSCRIPT (36) and raster3D (37).
Figure 4.
Fig. 4. Planar stacking of hydrophobic and Arg/Lys residues in domain 2 of the binding protein. The 2F[o]F[c]^ electron density map of the 1:2 complex is contoured at 1.0.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (1996, 271, 32197-32203) copyright 1996.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20575051 F.Mulinacci, S.E.Bell, M.A.Capelle, R.Gurny, and T.Arvinte (2011).
Oxidized recombinant human growth hormone that maintains conformational integrity.
  J Pharm Sci, 100, 110-122.  
20544968 D.J.Diller, C.Humblet, X.Zhang, and L.M.Westerhoff (2010).
Computational alanine scanning with linear scaling semiempirical quantum mechanical methods.
  Proteins, 78, 2329-2337.  
19927328 D.Poger, and A.E.Mark (2010).
Turning the growth hormone receptor on: evidence that hormone binding induces subunit rotation.
  Proteins, 78, 1163-1174.  
20238132 W.Q.Chen, A.Salmazo, M.Myllykoski, B.Sjöblom, M.Bidlingmaier, A.Pollak, P.Baumgärtel, K.Djinovic-Carugo, P.Kursula, and G.Lubec (2010).
Purification of recombinant growth hormone by clear native gels for conformational analyses: preservation of conformation and receptor binding.
  Amino Acids, 39, 859-869.  
19388064 S.Deechongkit, J.Wen, L.O.Narhi, Y.Jiang, S.S.Park, J.Kim, and B.A.Kerwin (2009).
Physical and biophysical effects of polysorbate 20 and 80 on darbepoetin alfa.
  J Pharm Sci, 98, 3200-3217.  
18080174 V.Borromeo, J.Sereikaite, V.A.Bumelis, C.Secchi, A.Scirè, A.Ausili, S.D'Auria, and F.Tanfani (2008).
Mink growth hormone structural-functional relationships: effects of renaturing and storage conditions.
  Protein J, 27, 170-180.  
16269515 J.F.Langenheim, D.Tan, A.M.Walker, and W.Y.Chen (2006).
Two wrongs can make a right: dimers of prolactin and growth hormone receptor antagonists behave as agonists.
  Mol Endocrinol, 20, 661-674.  
15208626 C.Dos Santos, L.Essioux, C.Teinturier, M.Tauber, V.Goffin, and P.Bougnères (2004).
A common polymorphism of the growth hormone receptor is associated with increased responsiveness to growth hormone.
  Nat Genet, 36, 720-724.  
12930995 S.T.Walsh, L.M.Jevitts, J.E.Sylvester, and A.A.Kossiakoff (2003).
Site2 binding energetics of the regulatory step of growth hormone-induced receptor homodimerization.
  Protein Sci, 12, 1960-1970.  
12843579 Y.Kurihara, T.Watanabe, H.Nojima, M.Takeda-Shitaka, H.Sumikawa, K.Kamiya, and H.Umeyama (2003).
Dynamic character of human growth hormone and its receptor: normal mode analysis.
  Chem Pharm Bull (Tokyo), 51, 754-758.  
12021444 A.V.Filikov, R.J.Hayes, P.Luo, D.M.Stark, C.Chan, A.Kundu, and B.I.Dahiyat (2002).
Computational stabilization of human growth hormone.
  Protein Sci, 11, 1452-1461.  
  9568895 D.K.Smith, and H.R.Treutlein (1998).
LIF receptor-gp130 interaction investigated by homology modeling: implications for LIF binding.
  Protein Sci, 7, 886-896.  
10089521 H.W.Christinger, P.A.Elkins, Y.Sandowski, E.Sakal, A.Gertler, A.A.Kossiakoff, and Vos (1998).
Crystallization of ovine placental lactogen in a 1:2 complex with the extracellular domain of the rat prolactin receptor.
  Acta Crystallogr D Biol Crystallogr, 54, 1408-1411.  
  9144766 R.J.Simpson, A.Hammacher, D.K.Smith, J.M.Matthews, and L.D.Ward (1997).
Interleukin-6: structure-function relationships.
  Protein Sci, 6, 929-955.  
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.