The Active Conformation of the PAK1 Kinase Domain

摘要: Summary The p21-activated kinases (PAKs) participate in cytoskeletal control networks, downstream of Rho-family GTPases. A structure PAK1 an autoregulated, "off" state showed that a regulatory region, N-terminal to the kinase domain, forces latter into inactive conformation, prevents phosphorylation Thr423 activation loop, and promotes dimerization. We have now determined structures at 1.8 resolution for free with mutation active site blocks enzymatic activity, same domain "phosphomimetic" loop. two very similar show even absence phosphorylated Thr423, has essentially conformation. When Cdc42 binds region dissociates dimer, will be "intermediate-active" state, capacity phosphorylate itself or other substrates prior modification its