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Hormone/growth factor
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PDB id
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2ask
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Contents |
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* Residue conservation analysis
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PDB id:
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Hormone/growth factor
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Title:
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Structure of human artemin
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Structure:
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Artemin. Chain: a, b. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Biol. unit:
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Dimer (from
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Resolution:
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1.55Å
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R-factor:
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0.231
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R-free:
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0.255
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Authors:
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L.Silvian,P.Jin,P.Carmillo,P.A.Boriack-Sjodin,C.Pelletier, M.Rushe,B.J.Gong,D.Sah,B.Pepinsky,A.Rossomando
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Key ref:
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L.Silvian
et al.
(2006).
Artemin crystal structure reveals insights into heparan sulfate binding.
Biochemistry,
45,
6801-6812.
PubMed id:
DOI:
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Date:
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23-Aug-05
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Release date:
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13-Jun-06
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PROCHECK
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Headers
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References
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Seq:
Struc:
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220 a.a.
101 a.a.
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Key: |
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PfamA domain |
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PfamB domain |
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Secondary structure |
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CATH domain |
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Gene Ontology (GO) functional annotation
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Biochemical function
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growth factor activity
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1 term
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DOI no:
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Biochemistry
45:6801-6812
(2006)
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PubMed id:
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Artemin crystal structure reveals insights into heparan sulfate binding.
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L.Silvian,
P.Jin,
P.Carmillo,
P.A.Boriack-Sjodin,
C.Pelletier,
M.Rushe,
B.Gong,
D.Sah,
B.Pepinsky,
A.Rossomando.
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ABSTRACT
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Artemin (ART) promotes the growth of developing peripheral neurons by signaling
through a multicomponent receptor complex comprised of a transmembrane tyrosine
kinase receptor (cRET) and a specific glycosylphosphatidylinositol-linked
co-receptor (GFRalpha3). Glial cell line-derived neurotrophic factor (GDNF)
signals through a similar ternary complex but requires heparan sulfate
proteoglycans (HSPGs) for full activity. HSPG has not been demonstrated as a
requirement for ART signaling. We crystallized ART in the presence of sulfate
and solved its structure by isomorphous replacement. The structure reveals
ordered sulfate anions bound to arginine residues in the pre-helix and
amino-terminal regions that were organized in a triad arrangement characteristic
of heparan sulfate. Three residues in the pre-helix were singly or triply
substituted with glutamic acid, and the resulting proteins were shown to have
reduced heparin-binding affinity that is partly reflected in their ability to
activate cRET. This study suggests that ART binds HSPGs and identifies residues
that may be involved in HSPG binding.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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M.M.Bespalov,
Y.A.Sidorova,
S.Tumova,
A.Ahonen-Bishopp,
A.C.Magalhães,
E.Kulesskiy,
M.Paveliev,
C.Rivera,
H.Rauvala,
and
M.Saarma
(2011).
Heparan sulfate proteoglycan syndecan-3 is a novel receptor for GDNF, neurturin, and artemin.
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J Cell Biol, 192,
153-169.
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P.Harvey,
B.Gong,
A.J.Rossomando,
and
E.Frank
(2010).
Topographically specific regeneration of sensory axons in the spinal cord.
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Proc Natl Acad Sci U S A, 107,
11585-11590.
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M.D.Wood,
G.H.Borschel,
and
S.E.Sakiyama-Elbert
(2009).
Controlled release of glial-derived neurotrophic factor from fibrin matrices containing an affinity-based delivery system.
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J Biomed Mater Res A, 89,
909-918.
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N.S.Gandhi,
and
R.L.Mancera
(2008).
The structure of glycosaminoglycans and their interactions with proteins.
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Chem Biol Drug Des, 72,
455-482.
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M.M.Bespalov,
and
M.Saarma
(2007).
GDNF family receptor complexes are emerging drug targets.
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Trends Pharmacol Sci, 28,
68-74.
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S.Schlee,
P.Carmillo,
and
A.Whitty
(2006).
Quantitative analysis of the activation mechanism of the multicomponent growth-factor receptor Ret.
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Nat Chem Biol, 2,
636-644.
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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.
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Links
