A Structural Basis for the Regulatory Inactivation of DnaA

作者：Xu Qingping; McMullan Daniel; Abdubek Polat; Astakhova Tamara; Carlton Dennis; Chen Connie; Chiu Hsiu Ju; Clayton Thomas; Das Debanu; Deller Marc C; Duan Lian; Elsliger Marc Andre; Feuerhelm Julie; Hale Joanna; Han Gye Won; Jaroszewski Lukasz; Jin Kevin K; Johnson Hope A; Klock Heath E; Knuth Mark W; Kozbial Piotr; Krishna S Sri; Kumar Abhinav; Marciano David; Miller Mitchell D; Morse Andrew T; Nigoghossian Edward; Nopakun Amanda; Okach Linda

来源：Journal of Molecular Biology, 2009, 385(2): 368-380.

DOI：10.1016/j.jmb.2008.10.059

• Hda
• DnaA
• RIDA
• AAA plus ATPase
• Structural Genomics

Regulatory inactivation of DnaA is dependent on Hda (homologous to DnaA), a protein homologous to the AAA (ATPases associated with diverse cellular activities) ATPase region of the replication initiator DnaA. When bound to the sliding clamp loaded onto duplex DNA, Hda can stimulate the transformation of active DnaA-ATP into inactive DnaA-ADP. The crystal structure of Hda from Shewanella amazonensis SB2B at 1.75 angstrom resolution reveals that Hda resembles typical AAA ATPases. The arrangement of the two subdomains in Hda (residues 1-174 and 175-241) differs dramatically from that of DnaA. A CDP molecule anchors the Hda domains in a conformation that promotes dimer formation. The Hda dimer adopts a novel oligomeric assembly for AAA proteins in which the arginine finger, crucial for ATP hydrolysis, is fully exposed and available to hydrolyze DnaA-ATP through a typical AAA type of mechanism. The sliding clamp binding motifs at the N-terminus of each Hda monomer are partially buried and combine to form an antiparallel beta-sheet at the dimer interface. The inaccessibility of the clamp binding motifs in the CDP-bound structure of Hda suggests that conformational changes are required for Hda to form a functional complex with the clamp. Thus, the CDP-bound Hda dimer likely represents an inactive form of Hda.

• 出版日期2009-1-16
• 单位河北医科大学