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  • ATP binds to proteasomal ATPases in pairs with distinct functional effects, implying an ordered reaction cycle.

ATP binds to proteasomal ATPases in pairs with distinct functional effects, implying an ordered reaction cycle.

Cell (2011-02-22)
David M Smith, Hugo Fraga, Christian Reis, Galit Kafri, Alfred L Goldberg
ABSTRACT

In the eukaryotic 26S proteasome, the 20S particle is regulated by six AAA ATPase subunits and, in archaea, by a homologous ring complex, PAN. To clarify the role of ATP in proteolysis, we studied how nucleotides bind to PAN. Although PAN has six identical subunits, it binds ATPs in pairs, and its subunits exhibit three conformational states with high, low, or no affinity for ATP. When PAN binds two ATPĪ³S molecules or two ATPĪ³S plus two ADP molecules, it is maximally active in binding protein substrates, associating with the 20S particle, and promoting 20S gate opening. However, binding of four ATPĪ³S molecules reduces these functions. The 26S proteasome shows similar nucleotide dependence. These findings imply an ordered cyclical mechanism in which two ATPase subunits bind ATP simultaneously and dock into the 20S. These results can explain how these hexameric ATPases interact with and "wobble" on top of the heptameric 20S proteasome.

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Sigma-Aldrich
Adenosine 5ā€²-[Ī³-thio]triphosphate tetralithium salt, ≥75% (HPLC), powder