Chaperones

Chaperones for assembly of remodeling complexes
The INO80 complex contains the hexameric AAA+ ATPases Rvb1 and Rvb2 in addition to a remodeling ATPase subunit Ino80 and several other subunits. The Rvbs are not found in SWI/SNF or ACF complexes. These AAA+ ATPases were originally thought to act as helicases. However the Rvb1/Rvb2 ATPases are found in a number of multi-subunit complexes unrelated to chromatin, such as snoRNP complexes, and telomerase. Recent work has provided evidence for Rvb1/Rvb2 complex acting as a complex assembly chaperone. A non-ATPase region within the ATPase subunit of the INO80 complex stimulates Rvbs’ ATPase activity by 16-fold while concomitantly promoting their dodecamerization. We are currently testing a model where binding of multiple protein clients like Ino80 stimulates ATP-driven cycling between hexamers and dodecamers, providing iterative opportunities for correct subunit assembly. We believe that the mechanistic insights derived from understanding the role of the Rvbs in INO80 function will help uncover how these essential AAA+ ATPases act as assembly chaperones for diverse multi-subunit complexes.