PDBsum entry: 1uap

Protein binding

PDB id: 1uap

Contents

Protein chain

131 a.a. *

* Residue conservation analysis

PDB id:

1uap

Name:

Protein binding

Title:

Nmr structure of the ntr domain from human pcolce1

Structure:

Procollagen c-proteinase enhancer protein. Chain: a. Fragment: ntr domain. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: pcolce. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

NMR struc:

20 models

Authors:

E.Liepinsh,L.Banyai,G.Pintacuda,M.Trexler,L.Patthy,G.Otting

Key ref:

E.Liepinsh et al. (2003). NMR structure of the netrin-like domain (NTR) of human type I procollagen C-proteinase enhancer defines structural consensus of NTR domains and assesses potential proteinase inhibitory activity and ligand binding. J Biol Chem, 278, 25982-25989. PubMed id: 12670942 DOI: 10.1074/jbc.M302734200

Date:

14-Mar-03 Release date: 15-Jul-03

Protein chain

Q15113  (PCOC1_HUMAN) -  Procollagen C-endopeptidase enhancer 1

Seq: 449 a.a.

Struc: 131 a.a.*

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

 Gene Ontology (GO) functional annotation 

• Biochemical function: protein binding (1 term)

DOI no: 10.1074/jbc.M302734200

J Biol Chem 278:25982-25989 (2003)

PubMed id: 12670942

NMR structure of the netrin-like domain (NTR) of human type I procollagen C-proteinase enhancer defines structural consensus of NTR domains and assesses potential proteinase inhibitory activity and ligand binding.

E.Liepinsh, L.Banyai, G.Pintacuda, M.Trexler, L.Patthy, G.Otting.

ABSTRACT

Procollagen C-proteinase enhancer (PCOLCE) proteins are extracellular matrix proteins that enhance the activities of procollagen C-proteinases by binding to the C-propeptide of procollagen I. PCOLCE proteins are built of three structural modules, consisting of two CUB domains followed by a C-terminal netrin-like (NTR) domain. While the enhancement of proteinase activity can be ascribed solely to the CUB domains, sequence homology of the NTR domain with tissue inhibitors of metalloproteinases suggest proteinase inhibitory activity for the NTR domain. Here we present the three-dimensional structure of the NTR domain of human PCOLCE1 as the first example of a structural domain with the canonical features of an NTR module. The structure rules out a binding mode to metalloproteinases similar to that of tissue inhibitors of metalloproteinases but suggests possible inhibitory function toward specific serine proteinases. Sequence conservation between 13 PCOLCE proteins from different organisms suggests a conserved binding surface for other protein partners.

Selected figure(s)

Figure 3.
FIG. 3. Solution structure of the NTR module of PCOLCE1 and comparison with the laminin-binding domain of agrin and TIMP-2. A, ribbon representation of the NTRPCOLCE1 module. Disulfide bonds are shown as yellow lines with spheres for the sulfur atoms. The -strands and -helices are numbered as in Fig. 1. White and yellow numbers distinguish strands and helices, respectively. B, ribbon representation of the laminin-binding domain from agrin (PDB code 1JC7 [PDB] ) (12). Secondary structure elements homologous to the NTRPCOLCE1 module are colored as in A. C, ribbon representation of TIMP-2 (PDB code 1BR9 [PDB] ) (30). Same coloring as in A, with the C-terminal segment, which has no counterpart in the NTRPCOLCE1 module, drawn in gray. D, stereo view of the NTRPCOLCE1 module, showing a superposition of the backbone atoms in the 20 conformers representing the NMR structure (Table I), in the same orientation as in A. The disulfide bonds are shown in yellow. Numbers identify sequence positions as in Fig. 1. E, stereo view of the NTRPCOLCE1 conformer closest to the mean structure of the 20 conformers shown in (D), using a heavy atom representation in an orientation rotated by 90^o around a horizontal axis. The polypeptide backbone is drawn in green. Backbone carbonyl groups and the flexible C-terminal four residues were omitted. The following colors were used for the side chains: blue, Arg, Lys, His; red, Glu, Asp; yellow, Ala, Cys, Ile, Leu, Met, Phe, Pro, Trp, Val; gray, Asn, Gln, Ser, Thr, Tyr. Heavy lines identify solvent-exposed residues conserved within the groups of mammalian PCOLCE1s, mammalian PCOLCE2s, fish PCOLCEs, and frog PCOLCEs (see text). Selected residues are labeled. Residues from a coherent patch of conserved and solvent-accessible side chains are labeled in red.

Figure 4.
FIG. 4. Comparison of the NTRPCOLCE1 domain with BPTI and PSTI. A, stereo view of backbone traces of the NTRPCOLCE1 domain (red) superimposed onto the trypsin inhibitors BPTI (cyan; PDB code 1BTH [PDB] ) (37) and PSTI (magenta; PDB code 1TGS [PDB] ) (38). The trypsinogen molecule present in the 1TGS [PDB] coordinate set is shown truncated (blue). The superposition of BPTI and PSTI was achieved by superposition of the proteinases in the BPTI·thrombin-E192Q and PSTI·trypsinogen complexes, respectively. The NTRPCOLCE1 domain was superimposed for best fit of the backbone surrounding Lys-32. The arrow identifies the P1 site in BPTI and PSTI. In addition, two selected residues in the NTRPCOLCE1 domain are labeled. B, stereo view of a superposition of the peptide segment 30-36 of the NTRPCOLCE1 domain (using the conformer closest to the mean structure in this segment; backbone in red), the proteinase-binding peptide segment 13-19 of BPTI (backbone in cyan), and the proteinase-binding peptide segment 16-22 of PSTI (backbone in magenta). The C^ atoms of the residues in the P1-P3 and P1'-P3' sites of the inhibitors are identified. Spheres mark the N- and C-atoms of the N- and C-terminal ends, respectively, of the polypeptide segments. The following colors were used for the side chains: blue, Arg, Lys; yellow, Ala, Cys, Ile, Pro; gray, Asn, Gln, Thr, Tyr. C, sequence alignment of the inhibitor segments shown in B. Boxes identify residues with closely superimposable backbones.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 25982-25989) copyright 2003.

Figures were selected by an automated process.