PDBsum entry 1axi

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protein ligands Protein-protein interface(s) links
Complex (hormone/receptor) PDB id
Protein chains
175 a.a. *
191 a.a. *
Waters ×382
* Residue conservation analysis
PDB id:
Name: Complex (hormone/receptor)
Title: Structural plasticity at the hgh:hghbp interface
Structure: Growth hormone. Chain: a. Synonym: hgh. Engineered: yes. Mutation: yes. Growth hormone receptor. Chain: b. Fragment: extracellular binding domain. Synonym: hghbp.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PQS)
2.10Å     R-factor:   0.190     R-free:   0.262
Authors: S.Atwell,M.Ultsch,A.M.De Vos,J.A.Wells
Key ref:
S.Atwell et al. (1997). Structural plasticity in a remodeled protein-protein interface. Science, 278, 1125-1128. PubMed id: 9353194 DOI: 10.1126/science.278.5340.1125
15-Oct-97     Release date:   28-Jan-98    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P01241  (SOMA_HUMAN) -  Somatotropin
217 a.a.
175 a.a.*
Protein chain
Pfam   ArchSchema ?
P10912  (GHR_HUMAN) -  Growth hormone receptor
638 a.a.
191 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 7 residue positions (black crosses)

 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: 10.1126/science.278.5340.1125 Science 278:1125-1128 (1997)
PubMed id: 9353194  
Structural plasticity in a remodeled protein-protein interface.
S.Atwell, M.Ultsch, A.M.De Vos, J.A.Wells.
Remodeling of the interface between human growth hormone (hGH) and the extracellular domain of its receptor was studied by deleting a critical tryptophan residue (at position 104) in the receptor, creating a large cavity, and selecting a pentamutant of hGH by phage display that fills the cavity and largely restores binding affinity. A 2.1 A resolution x-ray structure of the mutant complex showed that the receptor cavity was filled by selected hydrophobic mutations of hGH. Large structural rearrangements occurred in the interface at sites that were distant from the mutations. Such plasticity may be a means for protein-protein interfaces to adapt to mutations as they coevolve.
  Selected figure(s)  
Figure 1.
Fig. 1. Residues in hGHbp (rendered in pink or orange sticks) that contact hGH (in blue space-filling rendition) in the 1:1 wild-type^ complex (A) or the complex between A1-hGH and W104A-hGHbp (B). Local groups where hydrogen bonds are different between the complexes are shown as yellow dashed lines.
Figure 3.
Fig. 3. Two views (A and B) of nonmutated contact residues that change salt bridge partners in the A1-hGH and W104A-hGHbp complex (right) relative to the wild-type complex (left). Hormone^ residues are in blue, and receptor residues are in pink, except for position 104 which is in orange.
  The above figures are reprinted by permission from the AAAs: Science (1997, 278, 1125-1128) copyright 1997.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20018744 A.V.Smrcka, N.Kichik, T.Tarragó, M.Burroughs, M.S.Park, N.K.Itoga, H.A.Stern, B.M.Willardson, and E.Giralt (2010).
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Peptide-mediated liposomal drug delivery system targeting tumor blood vessels in anticancer therapy.
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Munc18-1 binding to the neuronal SNARE complex controls synaptic vesicle priming.
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  Structure, 12, 1489-1494.
PDB codes: 1u36 1u3j 1u3y 1u3z 1u41 1u42
15653425 E.J.Helmreich (2004).
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15211515 H.Gohlke, L.A.Kuhn, and D.A.Case (2004).
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15563602 S.T.Walsh, J.E.Sylvester, and A.A.Kossiakoff (2004).
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15289606 S.Y.Park, B.D.Beel, M.I.Simon, A.M.Bilwes, and B.R.Crane (2004).
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PDB code: 1u0s
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14527405 M.J.Boulanger, A.J.Bankovich, T.Kortemme, D.Baker, and K.C.Garcia (2003).
Convergent mechanisms for recognition of divergent cytokines by the shared signaling receptor gp130.
  Mol Cell, 12, 577-589.
PDB code: 1pvh
12582206 M.R.Arkin, M.Randal, W.L.DeLano, J.Hyde, T.N.Luong, J.D.Oslob, D.R.Raphael, L.Taylor, J.Wang, R.S.McDowell, J.A.Wells, and A.C.Braisted (2003).
Binding of small molecules to an adaptive protein-protein interface.
  Proc Natl Acad Sci U S A, 100, 1603-1608.
PDB codes: 1m47 1m48 1m49 1m4a 1m4b 1m4c
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.
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12021444 A.V.Filikov, R.J.Hayes, P.Luo, D.M.Stark, C.Chan, A.Kundu, and B.I.Dahiyat (2002).
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  Protein Sci, 11, 1452-1461.  
12112677 G.M.Verkhivker, D.Bouzida, D.K.Gehlhaar, P.A.Rejto, S.T.Freer, and P.W.Rose (2002).
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  Proteins, 48, 539-557.  
11807947 L.Jiang, Y.Gao, F.Mao, Z.Liu, and L.Lai (2002).
Potential of mean force for protein-protein interaction studies.
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Evolutionary predictions of binding surfaces and interactions.
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11913381 S.Huo, I.Massova, and P.A.Kollman (2002).
Computational alanine scanning of the 1:1 human growth hormone-receptor complex.
  J Comput Chem, 23, 15-27.  
12381794 T.Kortemme, and D.Baker (2002).
A simple physical model for binding energy hot spots in protein-protein complexes.
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Knowledge-based potential functions in protein design.
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11425742 H.C.Wu, C.T.Yeh, Y.L.Huang, L.J.Tarn, and C.C.Lung (2001).
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11754823 S.Radaev, B.Rostro, A.G.Brooks, M.Colonna, and P.D.Sun (2001).
Conformational plasticity revealed by the cocrystal structure of NKG2D and its class I MHC-like ligand ULBP3.
  Immunity, 15, 1039-1049.
PDB code: 1kcg
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Luxury accommodations: the expanding role of structural plasticity in protein-protein interactions.
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10704464 H.R.Churchill, P.S.Andersen, E.A.Parke, R.A.Mariuzza, and D.M.Kranz (2000).
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  J Exp Med, 191, 835-846.  
11058786 K.J.Kallen, J.Grötzinger, and S.Rose-John (2000).
New perspectives on the design of cytokines and growth factors.
  Trends Biotechnol, 18, 455-461.  
10672010 K.W.Rodenburg, F.Vallée, N.Juge, N.Aghajari, X.Guo, R.Haser, and B.Svensson (2000).
Specific inhibition of barley alpha-amylase 2 by barley alpha-amylase/subtilisin inhibitor depends on charge interactions and can be conferred to isozyme 1 by mutation.
  Eur J Biochem, 267, 1019-1029.  
10852948 T.J.Wandless (2000).
A confederacy of bunches: fundamentals and applications of a self-associating protein.
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10380930 J.H.Wang, A.Smolyar, K.Tan, J.H.Liu, M.Kim, Z.Y.Sun, G.Wagner, and E.L.Reinherz (1999).
Structure of a heterophilic adhesion complex between the human CD2 and CD58 (LFA-3) counterreceptors.
  Cell, 97, 791-803.
PDB code: 1qa9
  10348859 J.J.Caguiat, A.L.Watson, and A.O.Summers (1999).
Cd(II)-responsive and constitutive mutants implicate a novel domain in MerR.
  J Bacteriol, 181, 3462-3471.  
10631938 K.C.Garcia (1999).
Molecular interactions between extracellular components of the T-cell receptor signaling complex.
  Immunol Rev, 172, 73-85.  
10051576 R.Briesewitz, G.T.Ray, T.J.Wandless, and G.R.Crabtree (1999).
Affinity modulation of small-molecule ligands by borrowing endogenous protein surfaces.
  Proc Natl Acad Sci U S A, 96, 1953-1958.  
10449721 S.Atwell, and J.A.Wells (1999).
Selection for improved subtiligases by phage display.
  Proc Natl Acad Sci U S A, 96, 9497-9502.  
10398368 S.D.Nuttall, M.J.Rousch, R.A.Irving, S.E.Hufton, H.R.Hoogenboom, and P.J.Hudson (1999).
Design and expression of soluble CTLA-4 variable domain as a scaffold for the display of functional polypeptides.
  Proteins, 36, 217-227.  
10611645 S.N.Behncken, and M.J.Waters (1999).
Molecular recognition events involved in the activation of the growth hormone receptor by growth hormone.
  J Mol Recognit, 12, 355-362.  
  9732276 F.W.Whipple, E.F.Hou, and A.Hochschild (1998).
Amino acid-amino acid contacts at the cooperativity interface of the bacteriophage lambda and P22 repressors.
  Genes Dev, 12, 2791-2802.  
9724721 T.Clackson, W.Yang, L.W.Rozamus, M.Hatada, J.F.Amara, C.T.Rollins, L.F.Stevenson, S.R.Magari, S.A.Wood, N.L.Courage, X.Lu, F.Cerasoli, M.Gilman, and D.A.Holt (1998).
Redesigning an FKBP-ligand interface to generate chemical dimerizers with novel specificity.
  Proc Natl Acad Sci U S A, 95, 10437-10442.
PDB code: 1bl4
9729736 T.Clackson (1998).
Redesigning small molecule-protein interfaces.
  Curr Opin Struct Biol, 8, 451-458.  
9649307 W.Dall'Acqua, A.L.Simon, M.G.Mulkerrin, and P.Carter (1998).
Contribution of domain interface residues to the stability of antibody CH3 domain homodimers.
  Biochemistry, 37, 9266-9273.  
9628472 X.Ysern, H.Li, and R.A.Mariuzza (1998).
Imperfect interfaces.
  Nat Struct Biol, 5, 412-414.  
9707600 Y.Ghendler, M.K.Teng, J.H.Liu, T.Witte, J.Liu, K.S.Kim, P.Kern, H.C.Chang, J.H.Wang, and E.L.Reinherz (1998).
Differential thymic selection outcomes stimulated by focal structural alteration in peptide/major histocompatibility complex ligands.
  Proc Natl Acad Sci U S A, 95, 10061-10066.
PDB code: 1osz
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