ALPHA-HELICAL COILED-COIL OLIGOMERIZATION DOMAINS IN EXTRACELLULAR PROTEINS

Subunit oligomerization of many proteins is mediated by alpha-helical coiled-coil domains. 3,4-Hydrophobic heptad repeat sequences, the char acteristic feature of the coiled-coil protein folding motif, have been found in a wide variety of gene products including cytoskeletal, nucl ear, muscle, cell surface, extracellular, plasma, bacterial, and viral proteins. Whereas the majority of coiled-coil structures is represent ed by intracellular alpha-helical bundles that contain two polypeptide chains, examples of extracellular coiled-coil proteins are fewer in n umber. Most proteins located in the extracellular space form three-str anded alpha-helical assemblies. Recently, five-stranded coiled coils h ave been identified in thrombospondins 3 and 4 and in cartilage oligom eric matrix protein, and the formation of a heterotetramer has been ob served In in vitro studies with the recombinant asialoglycoprotein rec eptor oligomerization domain. Coiled-coil domains in laminins and prob ably also in tenascins and thrombospondins are responsible for the for mation of tissue-specific isoforms by selective oligomerization of dif ferent polypeptide chains.