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Publication Abstract from PubMed

The type III extra-domain B (ED-B) is specifically spliced into fibronectin (Fn) during embryogenesis and neoangiogenesis, including many cancers. The x-ray structure of the recombinant four-domain fragment Fn(III)7B89 reveals a tightly associated, extended head-to-tail dimer, which is stabilized via pair-wise shape and charge complementarity. A tendency toward ED-B-dependent dimer formation in solution was supported by size exclusion chromatography and analytical ultracentrifugation. When amending the model with the known three-dimensional structure of the Fn(III)10 domain, its RGD loop as well as the adhesion synergy region in Fn(III)9-10 become displayed on the same face of the dimer; this should allow simultaneous binding of at least two integrins and, thus, receptor clustering on the cell surface and intracellular signaling. Insertion of ED-B appears to stabilize overall head-to-tail dimerization of two separate Fn chains, which, together with alternating homodimer formation via disulfide bridges at the C-terminal Fn tail, should lead to the known macromolecular fibril formation.

Extra-domain B in Oncofetal Fibronectin Structurally Promotes Fibrillar Head-to-tail Dimerization of Extracellular Matrix Protein.,Schiefner A, Gebauer M, Skerra A J Biol Chem. 2012 May 18;287(21):17578-88. Epub 2012 Mar 22. PMID:22442152^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.