Structural basis for the recognition between the regulatory particles Nas6 and Rpt3 of the yeast 26S proteasome.

The 26S proteasome-dependent protein degradation is an evolutionarily conserved process. The mammalian oncoprotein gankyrin, which associates with S6 of the proteasome, facilitates the degradation of pRb, and thus possibly acts as a bridging factor between the proteasome and its substrates. However, the mechanism of the proteasome-dependent protein degradation in yeast is poorly understood. Here, we report the tertiary structure of the complex between Nas6 and a C-terminal domain of Rpt3, which are the yeast orthologues of gankyrin and S6, respectively. The concave region of Nas6 bound to the alpha-helical domain of Rpt3. The stable interaction between Nas6 and Rpt3 was mediated by intermolecular interactions composed of complementary charged patches. The recognition of Rpt3 by Nas6 in the crystal suggests that Nas6 is indeed a subunit of the 26S proteasome. These results provide a structural basis for the association between Nas6 and the heterohexameric ATPase ring of the proteasome through Rpt3.

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