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PMID: 9233787 Published · ppublish English Journal Article

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

The EMBO journal ·Vol. 16 ·No. 13 ·1997-07-01 ·Pages 3778-86

Hohenester E, Maurer P, Timpl R

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.

MeSH Terms
Agrin/chemistry Amino Acid Sequence Animals Binding Sites Calcium/metabolism Crystallography, X-Ray Epidermal Growth Factor/chemistry Factor IX/chemistry Follistatin Glycoproteins/chemistry,metabolism Humans Models, Molecular Molecular Sequence Data Osteonectin/chemistry,metabolism Ovomucin/chemistry Protein Structure, Secondary Rats Sequence Homology, Amino Acid Structure-Activity Relationship Trypsin Inhibitor, Kazal Pancreatic/chemistry
Chemicals
Agrin Follistatin Glycoproteins Osteonectin Ovomucin Trypsin Inhibitor, Kazal Pancreatic Epidermal Growth Factor Factor IX Calcium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hohenester E
Department of Crystallography, Birkbeck College, London, UK.
Maurer P
Timpl R
References (39)
39 references, click to expand
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/16.13.3778
Published
1997-07-01
Pages
3778-86
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1170001
Subset
IM
Databases
PDB
1BMO, R1BMOSF
External Links
PubMed source DOI: 10.1093/emboj/16.13.3778 PMC Full Text View journal details
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