MOLECULAR BIOLOGY OF THE EXTRACELLULAR MATRIX PROTEINS
Authors: KORNBLIHTT ALBERTO R. , GUTMAN ALEJANDRO 
Published: January 2008

Summary1. Extracellular matrices are organized networks of diverse macromolecules, secreted and deposited in the vicinity of cells. They not only play structural roles but are also involved in dynamic processes such as cell migration and differentiation, embryo development, wound healing and cancerous transformation. They are composed, mainly, of collagens, adhesive glycoproteins and proteoglycans, which interact with each other and with cell‐surface receptors through specific binding sites.2. Collagens are a multigenic family whose proteins have triple‐helical domains which contain repeats of the Gly‐X‐Y sequence. They aggregate to form fibrils, networks or filamentous structures. Gene organization reveals that fibril‐forming collagens might have originated from an ancestral 54 bp exon encoding 6 units of the Gly‐X‐Y triplet. Non‐fibrillar collagens, on the contrary, have evolved through different pathways which are not closely related to this mechanism.3. Fibronectins are dimers made up of three types of internal repeats: I, II and III. The first two are encoded by one exon each and have homologous counterparts in other proteins. Most of the type three repeats are encoded by two exons each. Cell‐specific alternative splicing in three different regions of the primary transcript generates, in humans, up to 20 polypeptide variants and explains structural differences between cellular and plasma fibronectins. Fibronectin interacts with its cell receptors through the sequence Arg‐Gly‐Asp.4. Laminin is a cross‐shaped molecule, characteristics of basement membranes, formed by three distinct polypeptides. Primary structure of one of its subunits reveals a repetitive organization with regions homologous to other proteins like myosin and epidermal growth factor. Laminin has a cell‐binding site, different from the Arg‐Gly‐Asp tripeptide, which is constituted by the sequence Tyr‐Ile‐Gly‐Ser‐Arg.5. Von Willebrand factor is a high‐molecular‐weight glycoprotein stored in specialized structures of platelets and endothelial cells. It participates in haemostatic mechanisms favouring the formation of the platelet plug. This protein has a particularly long propeptide and four types of internal homologies. It binds to two different platelet surface receptors, one of which interacts with an Arg‐Gly‐Asp sequence present in the von Willebrand polypeptide.6. Thrombospondin is an adhesive glycoprotein formed by three identical subunits which show striking homologies with Plasmodium proteins, epidermal growth factor and procollagen I. It also contains multiple calcium‐binding sites similar to those of calmodulin. An Arg‐Gly‐Asp sequence is also present, but its surface receptor has not yet been identified.7. Vitronectin is a glycoprotein, presumably involved in the process of blood coagulation, which is related to the extracellular matrix through binding to various of its components. It also binds to cell surfaces via an Arg‐Gly‐Asp sequence which is disrupted by a proteolytic cleavage that, concomitantly, originates somatomedin B, a peptide of unknown function.8. Proteoglycans are formed by glycosaminoglycan chains covalently bound to core proteins. They show a wide tissue distribution and structural variations. Most or all core proteins could possibly be synthesized as pre‐propolypeptides, and contain Ser‐Gly or Thr‐Gly repeats, which represent attachment sites for the glycosaminoglycans.9. A superfamily of cell‐surface receptors that recognizes RGD‐containing proteins is described. These receptors are intrinsic membrane proteins with large extracellular domains and an α/β heterodimeric structure. They are grouped in four families, each of them characterized by dimers which share a common β subunit and different α chains. Other receptors for extracellular matrix proteins that do not fit in the RGD superfamily are also reported.