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PDBsum entry 1ps2
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Growth factor
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PDB id
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1ps2
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References listed in PDB file
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Key reference
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Title
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High-Resolution solution structure of human pnr-2/ps2: a single trefoil motif protein.
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Authors
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V.I.Polshakov,
M.A.Williams,
A.R.Gargaro,
T.A.Frenkiel,
B.R.Westley,
M.P.Chadwick,
F.E.May,
J.Feeney.
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Ref.
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J Mol Biol, 1997,
267,
418-432.
[DOI no: ]
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PubMed id
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Abstract
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pNR-2/pS2 is a 60 residue extracellular protein, which was originally discovered
in human breast cancer cells, and subsequently found in other tumours and normal
gastric epithelial cells. We have determined the three-dimensional solution
structure of a C58S mutant of human pNR-2/pS2 using 639 distance and 137 torsion
angle constraints obtained from analysis of multidimensional NMR spectra. A
series of simulated annealing calculations resulted in the unambiguous
determination of the protein's disulphide bonding pattern and produced a family
of 19 structures consistent with the constraints. The peptide contains a single
"trefoil" sequence motif, a region of about 40 residues with a characteristic
sequence pattern, which has been found, either singly or as a repeat, in about a
dozen extracellular proteins. The trefoil domain contains three disulphide
bonds, whose 1-5, 2-4 and 3-6 cysteine pairings form the structure into three
closely packed loops with only a small amount of secondary structure, which
consists of a short alpha-helix packed against a two-stranded antiparallel
beta-sheet. The structure of the domain is very similar to those of the two
trefoil domains that occur in porcine spasmolytic polypeptide (PSP), the only
member of the trefoil family whose three-dimensional structure has been
previously determined. Outside the trefoil domain, which forms the compact
"head" of the molecule, the N and C-terminal strands are closely associated,
forming an extended "tail", which has some beta-sheet character for part of its
length and which becomes more disordered towards the termini as indicated by
(15)N{(1)H} NOEs. We have considered the structural implications of the possible
formation of a native C58-C58 disulphide-bonded homodimer. Comparison of the
surface features of pNR-2/pS2 and PSP, and consideration of the sequences of the
other human trefoil domains in the light of these structures, illuminates the
possible role of specific residues in ligand/receptor binding.
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Figure 1.
Figure 1. Summary of structural data versus residue number
(ticks on the horizontal axes mark every 10th residue). a, The
distribution of unambiguous NOE constraints for the residues of
pNR-2/pS2. Intraresidue, sequential, medium-(1<|i−j|<5) and
long-range (|i−j|>4) constraints are represented by black,
light grey, dark grey and white blocks, respectively. b, the
local 3 residue average rms difference for the heavy backbone
atoms (N, C^α and C) across the final family of structures
(Å). c, The measured ^15N{^1H} NOE values at 298 K and
14.1 Tesla (600 MHz for ^1H) for ^15N in the amide groups of
pNR-2/pS2. Lower values indicate higher mobility.
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Figure 5.
Figure 5. The amino acid sequence of pNR-2/pS2 aligned with
corresponding residues in the trefoil motifs of the mammalian
trefoil peptides PSP, hSP and hITF. The disulphide bonds and
secondary structure elements determined in this present work are
shown at the top of the diagram. Residues identical with those
in pNR-2/pS2 have been shaded in the diagram. A consensus
sequence motif derived from the mammalian trefoil peptides is
given at the bottom of the diagram. The sequences of porcine,
human, rat and mouse spasmolytic polypeptide, human and rat
intestinal trefoil factor, and human and mouse pS2 were used to
produce the consensus.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1997,
267,
418-432)
copyright 1997.
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Secondary reference #1
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Title
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Production and comparison of mature single-Domain 'Trefoil' Peptides pnr-2/ps2 cys58 and pnr-2/ps2 ser58.
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Authors
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M.P.Chadwick,
F.E.May,
B.R.Westley.
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Ref.
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Biochem J, 1995,
308,
1001-1007.
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PubMed id
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Secondary reference #2
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Title
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Nmr-Based structural studies of the pnr-2/ps2 single domain trefoil peptide. Similarities to porcine spasmolytic peptide and evidence for a monomeric structure.
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Authors
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V.I.Polshakov,
T.A.Frenkiel,
B.Westley,
M.Chadwick,
F.May,
M.D.Carr,
J.Feeney.
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Ref.
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Eur J Biochem, 1995,
233,
847-855.
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PubMed id
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