PDBsum entry 1bmo

Extracellular module

PDB id: 1bmo

Contents

Protein chain

233 a.a. *

Ligands

NAG-NAG ×2

Metals

_CA ×4

* Residue conservation analysis

PDB id:

1bmo

Name:

Extracellular module

Title:

Bm-40, fs/ec domain pair

Structure:

Bm-40. Chain: a, b. Fragment: fs/ec domain pair, residues 53 - 286. Synonym: sparc, osteonectin, basement membrane protein bm-40. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cell_line: 293. Organ: kidney. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293

Biol. unit:

Monomer (from PDB file)

Resolution:

3.10Å R-factor: 0.262 R-free: 0.322

Authors:

E.Hohenester,P.Maurer,R.Timpl

Key ref:

E.Hohenester et al. (1997). Crystal structure of a pair of follistatin-like and EF-hand calcium-binding domains in BM-40. Embo J, 16, 3778-3786. PubMed id: 9233787 DOI: 10.1093/emboj/16.13.3778

Date:

25-Mar-97 Release date: 15-Oct-97

Protein chains

P09486  (SPRC_HUMAN) -  SPARC from Homo sapiens

Seq: 303 a.a.

Struc: 233 a.a.

DOI no: 10.1093/emboj/16.13.3778

Embo J 16:3778-3786 (1997)

PubMed id: 9233787

Crystal structure of a pair of follistatin-like and EF-hand calcium-binding domains in BM-40.

E.Hohenester, P.Maurer, R.Timpl.

ABSTRACT

BM-40 (also known as SPARC or osteonectin) is an anti-adhesive secreted glycoprotein involved in tissue remodelling. Apart from an acidic N-terminal segment, BM-40 consists of a follistatin-like (FS) domain and an EF-hand calcium-binding (EC) domain. Here we report the crystal structure at 3.1 A resolution of the FS-EC domain pair of human BM-40. The two distinct domains interact through a small interface that involves the EF-hand pair of the EC domain. Residues implicated in cell binding, inhibition of cell spreading and disassembly of focal adhesions cluster on one face of BM-40, opposite the binding epitope for collagens and the N-linked carbohydrate. The elongated FS domain is structurally related to serine protease inhibitors of the Kazal family. Notable differences are an insertion into the inhibitory loop in BM-40 and a protruding N-terminal beta-hairpin with striking similarities to epidermal growth factor. This hairpin is likely to act as a rigid spacer in proteins containing tandemly repeated FS domains, such as follistatin and agrin, and forms the heparin-binding site in follistatin.

Selected figure(s)

Figure 1.
Figure 1 Stereo view (Kraulis, 1991) of the BM-40 FS -EC structure and its secondary structure elements. The FS domain (residues 54 -137) is shown in green and consists of an N-terminal -hairpin and a small hydrophobic core of / structure. The EC domain (residues 138 -286) is in red and consists of a pair of EF-hand calcium-binding sites and helices A, B and C. The calcium ions bound to the EF-hands are shown as yellow spheres. The FS and EC domains interact through a small interface involving mainly 5 and the preceding loop of the FS domain and E of the EC domain. The FS domain is glycosylated at Asn99; the first two N-acetylglucosamine (NAG) sugar moieties are included in the crystallographic model and are shown in atomic detail.

Figure 6.
Figure 6 Model of a tandem of FS domains in follistatin and agrin. The N-terminal domain (in green) and the C-terminal domain (in red) are linked by an extended segment of three residues (in blue); the relative rotation between the two domains is 0°. The tip of the N-terminal -hairpin of the C-terminal domain contacts the N-terminal domain at the small three-stranded -sheet and stabilizes the linear arrangement of domains. In this model, helix 2, which is unique to BM-40, has been replaced with the corresponding segment of ovomucoid (compare Figures 3 and 4A).

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: Embo J (1997, 16, 3778-3786) copyright 1997.

Figures were selected by an automated process.