PDBsum entry 1ps2

Growth factor

PDB id: 1ps2

Contents

Protein chain

60 a.a. *

* Residue conservation analysis

PDB id:

1ps2

Name:

Growth factor

Title:

High resolution nmr solution structure of human ps2, 19 structures

Structure:

Ps2. Chain: a. Synonym: pnr-2. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cell_line: hb101. Organ: breast, stomach. Tissue: epithelial. Cell: mcf-7, uacl. Cellular_location: extracellular. Gene: bcei.

NMR struc:

19 models

Authors:

M.A.Williams,V.I.Polshakov,A.R.Gargaro,J.Feeney

Key ref:

V.I.Polshakov et al. (1997). High-resolution solution structure of human pNR-2/pS2: a single trefoil motif protein. J Mol Biol, 267, 418-432. PubMed id: 9096235 DOI: 10.1006/jmbi.1997.0896

Date:

07-Jan-97 Release date: 07-Jul-97

Protein chain

P04155  (TFF1_HUMAN) -  Trefoil factor 1 from Homo sapiens

Seq: 84 a.a.

Struc: 60 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1006/jmbi.1997.0896

J Mol Biol 267:418-432 (1997)

PubMed id: 9096235

High-resolution solution structure of human pNR-2/pS2: a single trefoil motif protein.

V.I.Polshakov, M.A.Williams, A.R.Gargaro, T.A.Frenkiel, B.R.Westley, M.P.Chadwick, F.E.May, J.Feeney.

ABSTRACT

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.

Selected figure(s)

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.

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.

The above figures are reprinted by permission from Elsevier: J Mol Biol (1997, 267, 418-432) copyright 1997.

Figures were selected by an automated process.