ADDUCIN - A PHYSICAL MODEL WITH IMPLICATIONS FOR FUNCTION IN ASSEMBLYOF SPECTRIN-ACTIN COMPLEXES

Adducin binds to spectrin-actin complexes, promotes association of spe ctrin with actin, and is subject to regulation by calmodulin as well a s protein kinases A and C. Adducin is a heteromer comprised of homolog ous alpha- and beta-subunits with an NH2-terminal protease-resistant h ead domain, connected by a neck region to a COOH-terminal hydrophilic, protease-sensitive region, This study provides evidence that adducin in solution is a mixture of heterodimers and tetramers. CD spectroscop y of COOH-terminal domains of alpha- and beta-adducin bacterial recomb inants provides direct evidence for an unstructured random coil config uration, Cross-linking, proteolysis, and blot binding experiments sugg est a model for the adducin tetramer in which four head domains contac t one another to form a globular core with extended interacting alpha- and beta-adducin tails. The site for binding to spectrin-actin comple xes on adducin was identified as the COOH-terminal tail of both the al pha- and beta-adducin subunits. The capacity of native adducin to recr uit spectrin to actin filaments is similar to that of adducin tail dom ains. Thus, adducin tail domains alone are sufficient to interact with F-actin and a single spectrin and to recruit additional spectrin mole cules to the ternary complex.