AAA proteins: in search of a common molecular basis

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Abstract
The ‘International Meeting on Cellular Functions of AAA Proteins’ organized by Koreaki Ito and Teru Ogura took place in Kyoto, Jaoan, March 13–16, 2001. ![][1] The AAA proteins, members of the larger AAA+ superfamily, are a family of enzymatic machines involved in diverse cellular functions ranging from DNA repair and replication to organelle biogenesis, membrane trafficking, transcriptional regulation, and protein quality control. AAA proteins were defined as ATPases associated with various cellular activities, but this definition disguises the breadth and importance of their functions and the common structures and mechanisms of action that underlie their activities. At the International meeting on the cellular functions of AAA proteins in Kyoto, Japan, the organizers asked participants to come up with ‘a common molecular basis’ for understanding these proteins. The response was an impressive display that establishes the AAA proteins, alongside G proteins, as mediators of assembly and disassembly of macromolecular complexes. ### Structure—a motor within a machine AAA proteins do a lot of heavy work in the cell: erecting or disassembling complexes, unfolding or unwinding macromolecules, and transporting cellular cargo. This mechanical work requires a chemo‐mechanical converter, the AAA module, which derives its energy from ATP hydrolysis. AAA modules are composed of 200–250 amino acids predicted to have conserved secondary structures (Neuwald et al ., 1999). The motor module is attached to other domains that act as tool heads, the latter interacting with substrates either directly or through ‘adaptor’ molecules. The connectors between the motor and the tool heads thus act as coupling devices, akin to cams, converting movements of the motor into the specialized motion required for a particular activity. Several new crystal structures discussed at the meeting, together with previously resolved structures of the D2 domain of N ‐ethyl maleimide‐sensitive factor (NSF) (Lenzen et al ., 1998) and the δ′ subunit of the DNA clamp loader … [1]: pending:yes