title: Anastellin, an FN3 fragment with fibronectin polymerization activity, resembles amyloid fibril precursors.
abstract: Anastellin is a carboxy-terminal fragment of the first FN3 domain from human fibronectin. It is capable of polymerizing fibronectin in vitro, and it displays anti-tumor, anti-metastatic and anti-angiogenic properties in vivo. We have determined the structure of anastellin using nuclear magnetic resonance spectroscopy and identified residues critical for its activity. Anastellin exhibits dynamic fluctuations and conformational exchange in solution. Its overall topology is very similar to the corresponding region of full-length FN3 domains. However, its hydrophobic core becomes solvent-accessible and some of its beta-strands lose their protection against hydrogen bonding to beta-strands from other molecules. These features seem to be relevant for the fibronectin polymerization activity of anastellin and resemble the characteristics of amyloid fibril precursors. We suggest that this analogy is not random and may reflect similarities between fibronectin and amyloid fibril formation.
authors.affiliation: The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037-1062, USA.
authors.forename: Klára
authors.initials: K
authors.lastname: Briknarová
authors.forename: Maria E
authors.initials: ME
authors.lastname: Akerman
authors.forename: David W
authors.initials: DW
authors.lastname: Hoyt
authors.forename: Erkki
authors.initials: E
authors.lastname: Ruoslahti
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Ely
mesh_terms: D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry*; D002793:Cholic Acids / Q000737:chemistry; D003902:Detergents / Q000737:chemistry; D005353:Fibronectins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D013499:Surface Properties
chemical_list: D016564:Amyloid beta-Protein Precursor; D002793:Cholic Acids; D003902:Detergents; D005353:Fibronectins; D010446:Peptide Fragments; C423921:anastellin; C028213:3-((3-cholamidopropyl)dimethylammonium)-1-propanesulfonate