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PDBsum entry 1imx
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Hormone/growth factor
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PDB id
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1imx
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Contents |
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* Residue conservation analysis
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DOI no:
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Biochemistry
40:11022-11029
(2001)
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PubMed id:
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Crystal structure of human insulin-like growth factor-1: detergent binding inhibits binding protein interactions.
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F.F.Vajdos,
M.Ultsch,
M.L.Schaffer,
K.D.Deshayes,
J.Liu,
N.J.Skelton,
A.M.de Vos.
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ABSTRACT
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Despite efforts spanning considerably more than a decade, a high-resolution view
of the family of proteins known as insulin-like growth factors (IGFs) has
remained elusive. IGF-1 consists of three helical segments which are connected
by a 12-residue linker known as the C-region. NMR studies of members of this
family reveal a dynamic structure with a topology resembling insulin but little
structural definition in the C-region. We have crystallized IGF-1 in the
presence of the detergent deoxy big CHAPS, and determined its structure at 1.8 A
resolution by multiwavelength anomalous diffraction, exploiting the anomalous
scattering of a single bromide ion and six of the seven sulfur atoms of IGF-1.
The structure reveals a well-defined conformation for much of the C-region,
which extends away from the core of IGF-1 and has residues known to be involved
in receptor binding prominently displayed in a type II beta-turn. In the
crystal, these residues form a dimer interface, but analytical
ultracentrifugation experiments demonstrate that at physiological concentrations
IGF-1 is monomeric. A single detergent molecule contacts residues known to be
important for IGF-1 binding protein (IGFBP) interactions. Biophysical and
biochemical data show that the detergent binds to IGF-1 specifically and blocks
binding of IGFBP-1 and IGFBP-3.
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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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K.Prymula,
K.Sałapa,
and
I.Roterman
(2010).
"Fuzzy oil drop" model applied to individual small proteins built of 70 amino acids.
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J Mol Model,
16,
1269-1282.
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M.Liu,
Z.L.Wan,
Y.C.Chu,
H.Aladdin,
B.Klaproth,
M.Choquette,
Q.X.Hua,
R.B.Mackin,
J.S.Rao,
P.De Meyts,
P.G.Katsoyannis,
P.Arvan,
and
M.A.Weiss
(2009).
Crystal structure of a "nonfoldable" insulin: impaired folding efficiency despite native activity.
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J Biol Chem,
284,
35259-35272.
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PDB code:
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Z.Y.Guo,
Z.S.Qiao,
and
Y.M.Feng
(2008).
The in vitro oxidative folding of the insulin superfamily.
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Antioxid Redox Signal,
10,
127-140.
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J.V.Nauman,
P.G.Campbell,
F.Lanni,
and
J.L.Anderson
(2007).
Diffusion of insulin-like growth factor-I and ribonuclease through fibrin gels.
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Biophys J,
92,
4444-4450.
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E.Glaser,
S.Nilsson,
and
S.Bhushan
(2006).
Two novel mitochondrial and chloroplastic targeting-peptide-degrading peptidasomes in A. thaliana, AtPreP1 and AtPreP2.
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Biol Chem,
387,
1441-1447.
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P.Roche,
J.Brown,
A.Denley,
B.E.Forbes,
J.C.Wallace,
E.Y.Jones,
and
R.M.Esnouf
(2006).
Computational model for the IGF-II/IGF2r complex that is predictive of mutational and surface plasmon resonance data.
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Proteins,
64,
758-768.
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Q.X.Hua,
J.P.Mayer,
W.Jia,
J.Zhang,
and
M.A.Weiss
(2006).
The folding nucleus of the insulin superfamily: a flexible peptide model foreshadows the native state.
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J Biol Chem,
281,
28131-28142.
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Q.X.Hua,
M.Liu,
S.Q.Hu,
W.Jia,
P.Arvan,
and
M.A.Weiss
(2006).
A conserved histidine in insulin is required for the foldability of human proinsulin: structure and function of an ALAB5 analog.
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J Biol Chem,
281,
24889-24899.
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PDB code:
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A.Denley,
L.J.Cosgrove,
G.W.Booker,
J.C.Wallace,
and
B.E.Forbes
(2005).
Molecular interactions of the IGF system.
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Cytokine Growth Factor Rev,
16,
421-439.
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I.Siwanowicz,
G.M.Popowicz,
M.Wisniewska,
R.Huber,
K.P.Kuenkele,
K.Lang,
R.A.Engh,
and
T.A.Holak
(2005).
Structural basis for the regulation of insulin-like growth factors by IGF binding proteins.
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Structure,
13,
155-167.
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PDB code:
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K.Huang,
J.Dong,
N.B.Phillips,
P.R.Carey,
and
M.A.Weiss
(2005).
Proinsulin is refractory to protein fibrillation: topological protection of a precursor protein from cross-beta assembly.
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J Biol Chem,
280,
42345-42355.
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Y.Chen,
R.Jin,
H.Y.Dong,
and
Y.M.Feng
(2004).
In vitro refolding/unfolding pathways of amphioxus insulin-like peptide: implications for folding behavior of insulin family proteins.
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J Biol Chem,
279,
55224-55233.
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S.Lien,
and
H.B.Lowman
(2003).
Therapeutic peptides.
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Trends Biotechnol,
21,
556-562.
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X.Y.Jia,
Z.Y.Guo,
Y.Wang,
Y.Xu,
S.S.Duan,
and
Y.M.Feng
(2003).
Peptide models of four possible insulin folding intermediates with two disulfides.
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Protein Sci,
12,
2412-2419.
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K.Deshayes,
M.L.Schaffer,
N.J.Skelton,
G.R.Nakamura,
S.Kadkhodayan,
and
S.S.Sidhu
(2002).
Rapid identification of small binding motifs with high-throughput phage display: discovery of peptidic antagonists of IGF-1 function.
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Chem Biol,
9,
495-505.
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PDB code:
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P.De Meyts,
and
J.Whittaker
(2002).
Structural biology of insulin and IGF1 receptors: implications for drug design.
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Nat Rev Drug Discov,
1,
769-783.
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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.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
