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PDBsum entry 2gh0
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protein ligands Protein-protein interface(s) links
Hormone/growth factor PDB id
2gh0

 

 

 

 

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Contents
Protein chains
100 a.a. *
200 a.a. *
Ligands
NAG-NAG-BMA-MAN-
MAN
NAG
Waters ×236
* Residue conservation analysis
PDB id:
2gh0
Name: Hormone/growth factor
Title: Growth factor/receptor complex
Structure: Artemin. Chain: c, d. Engineered: yes. Gdnf family receptor alpha-3. Chain: a, b. Synonym: gfr-alpha-3. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Gene: gfra3. Expression_system_taxid: 7111
Biol. unit: Tetramer (from PQS)
Resolution:
1.92Å     R-factor:   0.222     R-free:   0.263
Authors: X.Q.Wang
Key ref:
X.Wang et al. (2006). Structure of artemin complexed with its receptor GFRalpha3: convergent recognition of glial cell line-derived neurotrophic factors. Structure, 14, 1083-1092. PubMed id: 16765900 DOI: 10.1016/j.str.2006.05.010
Date:
24-Mar-06     Release date:   27-Jun-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q5T4W7  (ARTN_HUMAN) -  Artemin from Homo sapiens
Seq:
Struc: 		220 a.a.
100 a.a.*
Protein chains
Pfam   ArchSchema ?
O60609  (GFRA3_HUMAN) -  GDNF family receptor alpha-3 from Homo sapiens
Seq:
Struc: 		400 a.a.
200 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 

 
DOI no: 10.1016/j.str.2006.05.010 Structure 14:1083-1092 (2006)
PubMed id: 16765900  
 
 
Structure of artemin complexed with its receptor GFRalpha3: convergent recognition of glial cell line-derived neurotrophic factors.
X.Wang, R.H.Baloh, J.Milbrandt, K.C.Garcia.
 
  ABSTRACT  
 
Artemin (ARTN) is a member of the glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) which regulate the development and maintenance of many neuronal populations in the mammalian nervous system. Here we report the 1.92 A crystal structure of the complex formed between ARTN and its receptor GFRalpha3, which is the initiating step in the formation of a ternary signaling complex containing the shared RET receptor. It represents a new receptor-ligand interaction mode for the TGF-beta superfamily that reveals both conserved and specificity-determining anchor points for all GFL-GFRalpha pairs. In tandem with the complex structure, cellular studies using receptor chimeras implicate dyad-symmetric composite interfaces for recruitment and dimerization of RET, leading to intracellular signaling. These studies should facilitate the functional dissection of the specific versus pleiotropic roles of this system in neurobiology, as well as its exploitation for therapeutic applications.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. Ligand-Receptor Contacts between Artemin and GFRa3
(A) Molecular surfaces highlight the knob-in-hole complementarity between the protruding ARTN finger region (cyan) and the recessed center of a triangular spiral of a helices in GFRa3 D2 (deep salmon) formed by helices a1, a2, and a5.
(B) Interatomic contacts between ARTN and GFRa3, with the hydrophobic core of ARTN surrounded by a halo of polar interactions.
(C) Electrostatic footprints and complementarity of buried residues of ARTN on top of the GFRa3 surface.
(D) Electrostatic footprints and complementarity of buried residues of GFRa3 on top of the ARTN surface.
 
  The above figure is reprinted by permission from Cell Press: Structure (2006, 14, 1083-1092) copyright 2006.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20462488 A.P.Hinck (2010).
Class II cytokine common receptors: something old, something new.
  Structure, 18, 551-552.  
20375925 A.Warnecke, V.Scheper, I.Buhr, G.I.Wenzel, K.Wissel, G.Paasche, N.Berkingali, J.R.Jørgensen, T.Lenarz, and T.Stöver (2010).
Artemin improves survival of spiral ganglion neurons in vivo and in vitro.
  Neuroreport, 21, 517-521.  
20473317 S.Kjaer, S.Hanrahan, N.Totty, and N.Q.McDonald (2010).
Mammal-restricted elements predispose human RET to folding impairment by HSCR mutations.
  Nat Struct Mol Biol, 17, 726-731.
PDB code: 2x2u
19838198 L.K.Ely, S.Fischer, and K.C.Garcia (2009).
Structural basis of receptor sharing by interleukin 17 cytokines.
  Nat Immunol, 10, 1245-1251.
PDB code: 3jvf
19208630 V.Veverka, A.J.Henry, P.M.Slocombe, A.Ventom, B.Mulloy, F.W.Muskett, M.Muzylak, K.Greenslade, A.Moore, L.Zhang, J.Gong, X.Qian, C.Paszty, R.J.Taylor, M.K.Robinson, and M.D.Carr (2009).
Characterization of the Structural Features and Interactions of Sclerostin: MOLECULAR INSIGHT INTO A KEY REGULATOR OF Wnt-MEDIATED BONE FORMATION.
  J Biol Chem, 284, 10890-10900.
PDB code: 2k8p
18541656 B.Lu, and M.PereiraPerrin (2008).
A novel immunoprecipitation strategy identifies a unique functional mimic of the glial cell line-derived neurotrophic factor family ligands in the pathogen Trypanosoma cruzi.
  Infect Immun, 76, 3530-3538.  
18353777 D.Sjöstrand, and C.F.Ibáñez (2008).
Insights into GFRalpha1 regulation of neural cell adhesion molecule (NCAM) function from structure-function analysis of the NCAM/GFRalpha1 receptor complex.
  J Biol Chem, 283, 13792-13798.  
18837980 J.J.Vamathevan, S.Hasan, R.D.Emes, H.Amrine-Madsen, D.Rajagopalan, S.D.Topp, V.Kumar, M.Word, M.D.Simmons, S.M.Foord, P.Sanseau, Z.Yang, and J.D.Holbrook (2008).
The role of positive selection in determining the molecular cause of species differences in disease.
  BMC Evol Biol, 8, 273.  
18465789 J.P.Cao, J.K.Yu, C.Li, Y.Sun, H.H.Yuan, H.J.Wang, and D.S.Gao (2008).
Integrin beta1 is involved in the signaling of glial cell line-derived neurotrophic factor.
  J Comp Neurol, 509, 203-210.  
18200608 O.Okhrimenko, and I.Jelesarov (2008).
A survey of the year 2006 literature on applications of isothermal titration calorimetry.
  J Mol Recognit, 21, 1.  
18845535 V.Parkash, V.M.Leppänen, H.Virtanen, J.M.Jurvansuu, M.M.Bespalov, Y.A.Sidorova, P.Runeberg-Roos, M.Saarma, and A.Goldman (2008).
The Structure of the Glial Cell Line-derived Neurotrophic Factor-Coreceptor Complex: INSIGHTS INTO RET SIGNALING AND HEPARIN BINDING.
  J Biol Chem, 283, 35164-35172.
PDB code: 2v5e
17322291 D.Sjöstrand, J.Carlsson, G.Paratcha, B.Persson, and C.F.Ibáñez (2007).
Disruption of the GDNF binding site in NCAM dissociates ligand binding and homophilic cell adhesion.
  J Biol Chem, 282, 12734-12740.  
17213820 J.Yang, P.Runeberg-Roos, V.M.Leppänen, and M.Saarma (2007).
The mouse soluble GFRalpha4 receptor activates RET independently of its ligand persephin.
  Oncogene, 26, 3892-3898.  
17218019 M.M.Bespalov, and M.Saarma (2007).
GDNF family receptor complexes are emerging drug targets.
  Trends Pharmacol Sci, 28, 68-74.  
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.

 

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