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Gene Ontology (GO) functional annotation
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Cellular component
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extracellular region
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1 term
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Biochemical function
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hormone activity
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1 term
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DOI no:
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J Mol Biol
253:749-758
(1995)
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PubMed id:
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Three-dimensional solution structure of bombyxin-II an insulin-like peptide of the silkmoth Bombyx mori: structural comparison with insulin and relaxin.
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K.Nagata,
H.Hatanaka,
D.Kohda,
H.Kataoka,
H.Nagasawa,
A.Isogai,
H.Ishizaki,
A.Suzuki,
F.Inagaki.
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ABSTRACT
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The three-dimensional solution structure of bombyxin-II, an insulin-like
two-chain peptide produced by the brain of the silkworm Bombyx mori, has been
determined by simulated annealing calculations based on 535 distance constraints
and 24 torsion-angle constraints derived from NMR data and three distance
constraints of the disulfide bonds. To our knowledge, this is the first
three-dimensional structure determined for an invertebrate insulin-related
peptide. The root-mean-square deviations between the best 10 structures and the
mean structure are 0.58(+/- 0.15) A for the backbone heavy atoms (N, C alpha, C)
and 1.03(+/- 0.18) A for all non-hydrogen atom if less well-defined N and C
termini (A1, A20, B(-2) to B4 and B23 to B25) are excluded. The overall
main-chain structure of bombyxin-II is similar to that of insulin. However,
there are significant conformational and functional differences in their B-chain
C-terminal parts. The B-chain C-terminal part of bombyxin-II adopts an extension
of the B-chain central helix like that of relaxin and is not required for
bombyxin activity, while the corresponding part of insulin adopts a sharp turn
and a beta-strand and is essential for insulin activity. This structure
demonstrates that bombyxin-II is more closely related to relaxin than to
insulin, and suggests that insulin might have evolved the additional
receptor-recognition site in the B-chain C-terminal beta-strand to distinguish
itself from bombyxin and relaxin. The structure of bombyxin-II thus provides
novel insights into the receptor recognition and divergent molecular evolution
of insulin-superfamily peptides.
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Selected figure(s)
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Figure 5.
Figure 5. Comparison of the
solution structure of bombyxin-II
with the solution structure of hu-
man insulin (Brookhaven Protein
Data Bank entry 1HIU; Hua et al.
1991) and crystal structure of hu-
man relaxin 2 (6RLX; Eigenbrot et al.
1991). wSchematic representation of
the main-chain fold (figure created
with Molscript; Kraulis, 1991). The
A-chain is shown in red and the
B-chain in green.
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Figure 6.
Figure 6. Comparison of the
proposed receptor-recognition sur-
face (viewed from the left side of
Figures 4 and 5). Space-filling
model. All non-hydrogen atoms are
shown. A, Distribution of side-chain
functional groups. The acidic, basic,
polar and hydrophobic residues are
colored in red, blue, yellow and
green, respectively. The Arg
residues at B9 and B13 in bombyxin-
II and human relaxin 2 are exposed
on the B-chain helix. B, Locked and
unlocked states. The solution
structure of human insulin (Brook-
haven Protein Data Bank entry
1HIU; Hua et al. 1991) corresponds
to the locked, inactive state,
while the solution structure of
[GlyB24]human insulin (1HIT; Hua
et al. 1991) represents a model of the
unlocked, active state (Hua et al. 1991). The solution structure of bombyxin-II and the crystal structure of human relaxin
2 (6RLX; Eigenbrot et al. 1991) correspond to the unlocked state. The hydrophobic surface is exposed in the unlocked
state, while it is covered by the B-chain C-terminal section in the locked state. The B-chain C-terminal segments (from
the residues at B20 to the C termini) are colored in yellow; the hydrophobic residues at A2 and A3 in light green; the
other hydrophobic core residues in purple and other residues in light blue.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1995,
253,
749-758)
copyright 1995.
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Figures were
selected
by an automated process.
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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.Nagata
(2010).
Studies of the structure-activity relationships of peptides and proteins involved in growth and development based on their three-dimensional structures.
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Biosci Biotechnol Biochem, 74,
462-470.
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J.Zhang,
and
M.Takeda
(2007).
Molecular characterization of MbADGF, a novel member of the adenosine deaminase-related growth factor in the cabbage armyworm, Mamestra brassicae: the functional roles in the midgut cell proliferation.
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Insect Mol Biol, 16,
351-360.
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S.Nagata,
H.Kataoka,
and
A.Suzuki
(2005).
Silk moth neuropeptide hormones: prothoracicotropic hormone and others.
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Ann N Y Acad Sci, 1040,
38-52.
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T.Yamazaki,
M.Takaoka,
E.Katoh,
K.Hanada,
M.Sakita,
K.Sakata,
Y.Nishiuchi,
and
H.Hirano
(2003).
A possible physiological function and the tertiary structure of a 4-kDa peptide in legumes.
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Eur J Biochem, 270,
1269-1276.
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PDB code:
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A.A.Claasz,
C.P.Bond,
R.A.Bathgate,
L.Otvos,
N.F.Dawson,
R.J.Summers,
G.W.Tregear,
and
J.D.Wade
(2002).
Relaxin-like bioactivity of ovine Insulin 3 (INSL3) analogues.
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Eur J Biochem, 269,
6287-6293.
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D.R.Nässel
(2002).
Neuropeptides in the nervous system of Drosophila and other insects: multiple roles as neuromodulators and neurohormones.
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Prog Neurobiol, 68,
1.
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Z.Y.Guo,
L.Shen,
and
Y.M.Feng
(2002).
The different folding behavior of insulin and insulin-like growth factor 1 is mainly controlled by their B-chain/domain.
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Biochemistry, 41,
1556-1567.
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Z.S.Qiao,
Z.Y.Guo,
and
Y.M.Feng
(2001).
Putative disulfide-forming pathway of porcine insulin precursor during its refolding in vitro.
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Biochemistry, 40,
2662-2668.
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G.Fullbright,
and
E.E.Büllesbach
(2000).
The receptor binding conformation of bombyxin is induced by alanine(B15).
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Biochemistry, 39,
9718-9724.
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S.H.Nakagawa,
H.S.Tager,
and
D.F.Steiner
(2000).
Mutational analysis of invariant valine B12 in insulin: implications for receptor binding.
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Biochemistry, 39,
15826-15835.
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E.E.Büllesbach
(1999).
Bombyxin exhibits an insulin-like response to modification in the N-terminal region of the A chain.
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J Pept Res, 54,
12-17.
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R.Sowdhamini,
D.F.Burke,
J.F.Huang,
K.Mizuguchi,
H.A.Nagarajaram,
N.Srinivasan,
R.E.Steward,
and
T.L.Blundell
(1998).
CAMPASS: a database of structurally aligned protein superfamilies.
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Structure, 6,
1087-1094.
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G.Fullbright,
E.R.Lacy,
and
E.E.Büllesbach
(1997).
The prothoracicotropic hormone bombyxin has specific receptors on insect ovarian cells.
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Eur J Biochem, 245,
774-780.
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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
