title: Solution structure of a pair of fibronectin type 1 modules with fibrin binding activity.
abstract: The tertiary structure of the fourth and fifth type 1 module pair from the N terminus of human fibronectin, has been determined by two-dimensional homonuclear 1H nuclear magnetic resonance (NMR) spectroscopy. Comparison of each module fold with those of two other type 1 modules shows that the type 1 "consensus" structure is conserved in the pair. The modules connect end-to-end to form an elongated structure with a limited clockwise twist around the long axis, from N to C terminus. The short five residue linker sequence forms a tight loop and the relative orientation of the two modules is maintained by fixed and intimate hydrophobic contacts, dominated by a non-conserved tryptophan residue from the fourth type 1 module. The protein binds specifically to fibrin in an ELISA and surface accessible residues that may be involved in this and other protein interactions can be identified. The structure provides an insight into how chains of type 1 modules may link up in intact fibronectin.
authors.affiliation: Department of Biochemistry, University of Oxford, U.K.
authors.forename: M J
authors.initials: MJ
authors.lastname: Williams
authors.forename: I
authors.initials: I
authors.lastname: Phan
authors.forename: T S
authors.initials: TS
authors.lastname: Harvey
authors.forename: A
authors.initials: A
authors.lastname: Rostagno
authors.forename: L I
authors.initials: LI
authors.lastname: Gold
authors.forename: I D
authors.initials: ID
authors.lastname: Campbell
mesh_terms: D000595:Amino Acid Sequence; D003196:Computer Graphics; D004797:Enzyme-Linked Immunosorbent Assay; D005337:Fibrin / Q000378:metabolism*; D005353:Fibronectins / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D012996:Solutions; D013329:Structure-Activity Relationship
chemical_list: D005353:Fibronectins; D012996:Solutions; D005337:Fibrin