Taxonomic distribution of proteins containing FN3 domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing FN3 domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

2.0 A crystal structure of a four-domain segment of human fibronectin encompassing the RGD loop and synergy region.

Leahy DJ, Aukhil I, Erickson HP
Cell. 1996; 84: 155-64

We have determined the 2.0 A crystal structure of a fragment of human fibronectin encompassing the seventh through the RGD-containing tenth type III repeats (FN7-10). The structure reveals an extended rod-like molecule with a long axis of approximately 140 A and highly variable relationships between adjacent domains. An unusually small rotation between domains 9 and 10 creates a distinctive binding site, in which the RGD loop from domain 10 and the "synergy" region from domain 9 are on the same face of FN7-10 and thus easily accessible to a single integrin molecule. The cell-binding RGD loop is well-ordered in this structure and extends approximately 10 A away from the FN7-10 core.

Crystal structure of tandem type III fibronectin domains from Drosophila neuroglian at 2.0 A.

Huber AH, Wang YM, Bieber AJ, Bjorkman PJ
Neuron. 1994; 12: 717-31

We report the crystal structure of two adjacent fibronectin type III repeats from the Drosophila neural cell adhesion molecule neuroglian. Each domain consists of two antiparallel beta sheets and is folded topologically identically to single fibronectin type III domains from the extracellular matrix proteins tenascin and fibronectin. beta bulges and left-handed polyproline II helices disrupt the regular beta sheet structure of both neuroglian domains. The hydrophobic interdomain interface includes a metal-binding site, presumably involved in stabilizing the relative orientation between domains and predicted by sequence comparision to be present in the vertebrate homolog molecule L1. The neuroglian domains are related by a near perfect 2-fold screw axis along the longest molecular dimension. Using this relationship, a model for arrays of tandem fibronectin type III repeats in neuroglian and other molecules is proposed.

Fibronectin structure and assembly.

Potts JR, Campbell ID
Curr Opin Cell Biol. 1994; 6: 648-55

Significant progress has been made recently in the determination of the structure and assembly of the important matrix protein fibronectin, a molecule mainly constructed from three modular units denoted Fn1, Fn2 and Fn3. Atomic resolution structures are now available for all three single modules, for Fn1 and Fn3 module pairs, and for the disulphide-linked join between fibronectin monomers. Combined with results from new binding and mutation studies, the new structural information is leading to a clearer view of structure/function relationships in intact fibronectin.

Collagen-binding recombinant fibronectin fragments containing type II domains.

Skorstengaard K, Holtet TL, Etzerodt M, Thogersen HC
FEBS Lett. 1994; 343: 47-50

Each of the two type II domains and four larger fragments, containing one or two type II domains of fibronectin, have been expressed in Escherichia coli. A special vector, containing a fragment encoding the cleavage site for Factor Xa, Ile-Glu-Gly-Arg, inserted immediately before the protein fragment of interest, was used. After treatment of the purified fusion proteins with reduced/oxidized glutathione, the correctly folded fibronectin fragments were released by proteolytic digestion with Factor Xa. The largest fragment, consisting of two type II and two type I domains, was the only fragment able to bind to immobilized gelatin.

Structure of a fibronectin type III domain from tenascin phased by MAD analysis of the selenomethionyl protein.

Leahy DJ, Hendrickson WA, Aukhil I, Erickson HP
Science. 1992; 258: 987-91

Fibronectin type III domains are found in many different proteins including cell surface receptors and cell adhesion molecules. The crystal structure of one such domain from the extracellular matrix protein tenascin was determined. The structure was solved by multiwavelength anomalous diffraction (MAD) phasing of the selenomethionyl protein and has been refined to 1.8 angstrom resolution. The folding topology of this domain is identical to that of the extracellular domains of the human growth hormone receptor, the second domain of CD4, and PapD. Although distinct, this topology is similar to that of immunoglobulin constant domains. An Arg-Gly-Asp (RGD) sequence that can function for cell adhesion is found in a tight turn on an exposed loop.

The three-dimensional structure of the tenth type III module of fibronectin: an insight into RGD-mediated interactions.

Main AL, Harvey TS, Baron M, Boyd J, Campbell ID
Cell. 1992; 71: 671-8

The solution structure of the tenth type III module of fibronectin has been determined using nuclear magnetic resonance techniques. The molecule has a fold similar to that of immunoglobulin domains, with seven beta strands forming two antiparallel beta sheets, which pack against each other. Both beta sheets contribute conserved hydrophobic residues to a compact core. The topology is more similar to that of domain 2 of CD4, PapD, and the extracellular domain of the human growth hormone receptor than to that of immunoglobulin C domains. The module contains an Arg-Gly-Asp sequence known to be involved in cell adhesion. This tripeptide is solvent exposed and lies on a conformationally mobile loop between strands F and G, consistent with its cell adhesion function.

Partial primary structure of bovine plasma fibronectin: three types of internal homology.

Petersen TE, Thogersen HC, Skorstengaard K, Vibe-Pedersen K, Sahl P, Sottrup-Jensen L, Magnusson S
Proc Natl Acad Sci U S A. 1983; 80: 137-41

Location of a collagen-binding domain in fibronectin.

Balian G, Click EM, Bornstein P
J Biol Chem. 1980; 255: 3234-6

Preferential labeling of COOH-terminal sequences in newly synthesized fibronectin was achieved by short term incorporation of radiolabeled amino acids in the presence of pactamycin, an inhibitor of polypeptide chain initiation. The labeled fibronectin was then cleaved with cathepsin D under conditions that yield a large (137,000-dalton) fragment that lacks collagen-binding properties, and a smaller (72,000-dalton) fragment that retains the ability of fibronectin to bind to collagen. Determination of the relative specific radioactivities of the two fragments leads us to conclude that the collagen-binding domain in fibronectin is located in the NH2-terminal third of the polypeptide chain and not in a COOH-terminal region as previously indicated by other structural studies.