We have determined the structure of plasma fibronectin by electron microscopy of Shadowed specimens . The 440,000 molecular weight, dimeric molecule appears to be a long, thin, highly flexible strand . The contour length of the most extended molecules is 160 nm, but a distribution of lengths down to 120 nm was observed, indicating flexibility in extension as well as in bending. The average diameter of the strand is 2 nm and there are no large globular domains. The large fragments produced by limited digestion with plasmin are not globular domains but are segments of the strand, whose length corresponds to the molecular weight of the polypeptide chain. We conclude that each polypeptide chain of the dimeric molecule spans half the length of the strand, with their carboxyl termini joined at the center of the strand and their amino termini at the ends . This model is supported by images of fibronectinfibrinogen complexes, in which the fibrinogen is always attached to an end of the fibronectin strand .Fibronectin is a high molecular weight glycoprotein that is found in a soluble form in blood and other extracellular tissue fluids, and in an insoluble form in connective tissues and attached to cell surfaces . Fibronectin is thought to mediate the attachment of cells to the other components of the extracellular matrix, in particular to collagen and, where it occurs, fibrinogen or fibrin (for reviews see 14,16,22,26). Both plasma fibronectin and the cell surface or extracellular matrix forms are dimers, comprising two subunits of 220,000 mol wt, covalently linked by a single disulfide bond near their carboxyl termini . The two polypeptide chains are identical by most criteria but are frequently separated as a closely spaced doublet in gel electrophoresis ; the basis for this separation is not known (11) . Cell surface fibronectin differs from plasma fibronectin in carbohydrate content and solubility and exists as oligomers of the basic dimeric molecule, but the two forms are very similar in amino acid composition and are immunologically indistinguishable (14) .Plasma fibronectin has a sedimentation coefficient of 8 to 13S, depending on the pH and ionic strength (1) . This is too small for a globular protein of 440,000 mol wt, and suggests that the molecule has an elongated shape (1) . Studies with proteases have shown that fibronectin can be cleaved into a number of large fragments or domains, and it has been found that the different binding functions are retained by the separated domains . By analogy with the well established trinodular THE JOURNAL OF CELL BIOLOGY " VOLUME 91 DECEMBER 1981 673-678 © The Rockefeller University Press -0021-9525/81/12/0673/06 $1 .00 structure of fibrinogen, it has been suggested (1, 16) that fibronectin may have a nodular structure, consisting of large globular domains connected by flexible linking segments that can be readily attacked by proteases .Techniques of electron microscopy are now well established for determining the structure of large proteins . Molecular structures de...
