ABSTRACT
This chapter is concerned with details of the interactions between fibronectin and a widely distributed class of macromolecules termed "glycosaminoglycans" that usually are covalently linked to a polypeptide core forming complex structures known as proteoglycans. The most salient characteristic of all forms of fibronectin is the presence on each of its polypeptide chains of discrete regions capable of binding to one or more of a variety of biological molecules (Fig. 1). These properties in turn confer upon fibronectin its most prominent biological function as an adhesive macromolecule mediating attachments between cells (such as fibroblasts, macrophages, and bacteria), collagen, fibrin(ogen), glycosaminoglycans (heparan sulfate), and/or other biological substances. In trying to understand the biological behavior of fibronectin con <target id="page_78" target-type="page">78</target>Schematic model of the plasma fibronectin molecule showing the location of certain of the well-characterized binding domains. The model represents a composite drawn from literature cited or summarized in the text and here. Abbreviations used are NH2, amino terminus; COOH, carboxyl terminus; XL, factor XIIIa (plasma transglutaminase)-catalyzed cross-linking site; Fn-Fn, fibronectin self-assembly binding site; s-s, disulfide bridge; A, fibronectin A chain; B, fibronectin B chain. Other symbols are self-explanatory. The thin curved lines indicate protease-sensitive regions, cleavage at which yield the major proteolytic fragments containing the designated binding functions.
The NH2-terminal domain has sites that bind to actin [1], Staphylococcus aureus [2], fibrin [3,4], and heparin, the latter by a calcium-sensitive mechanism [5]. Adjacent to this domain lies the carbohydrate-rich collagen binding domain [6-11], which also contains a fibronectin self-association binding site [12]. Adjacent to this domain lies a cell binding domain [10,13] plus a weak heparin binding site [14] and a DNA binding site [15]. The remaining domains contain the heparin binding site of highest affinity (heparin II) as well as a second fibrin binding site (see text for details) plus a fibronectin self-association site [16] evidently complementary to the site in the collagen-binding domain. Finally, the dimeric chains of each molecule are held together by two disulfide bridges near the COOH terminus [11]. The A and B chains appear to differ from one another in that region of the molecule containing the heparin II and fibrin II binding sites (see text for details).
The heparin I (Ca2+ sensitive, intermediate affinity), and heparin II (high affinity, Ca2+ insensitive) sites have been characterized by several investigators (see text). A third binding site (heparin III) has weak affinity for heparin; its binding is inhibited by physiological concentrations of NaCl [14]. It is not certain whether this heparin binding site is the same as that described by Hayashi and Yamada [5].
https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781003065401/7c521f8c-d189-43b5-82b0-10c5a3b40ed5/content/fig5_1.tif"/> 79cerned with binding to glyeosammoglyeans, it is difficult and probably even undesirable to limit our considerations to just those specific interactions. Thus, although it is our intention to focus on structural and functional aspects of fibronectin-glycosaminoglycan interactions, we have tried to integrate these discussions, whenever warranted, to include consideration of other relevant binding functions of the molecule.