Subunit oligomerization of many proteins is mediated by alpha-helical coiled-coil domains. 3,4-Hydrophobic heptad repeat sequences, the characteristic feature of the coiled-coil protein folding motif, have been found in a wide variety of gene products including cytoskeletal, nuclear, muscle, cell surface, extracellular, plasma, bacterial, and viral proteins. Whereas the majority of coiled-coil structures is represented by intracellular alpha-helical bundles that contain two polypeptide chains, examples of extracellular coiled-coil proteins are fewer in number. Most proteins located in the extracellular space form three-stranded alpha-helical assemblies. Recently, five-stranded coiled coils have been identified in thrombospondins 3 and 4 and in cartilage oligomeric matrix protein, and the formation of a heterotetramer has been observed in in vitro studies with the recombinant asialoglycoprotein receptor oligomerization domain. Coiled-coil domains in laminins and probably also in tenascins and thrombospondins are responsible for the formation of tissue-specific isoforms by selective oligomerization of different polypeptide chains.