Rpt1Rpt6

Rpt1Rpt6 is the collective designation for the six ATPase subunits of the 19S regulatory particle base of the eukaryotic 26S proteasome. Rpt1 through Rpt6 are a family of closely related AAA+ ATPases that assemble as a heterohexameric ring. This ATPase ring sits at the base of the regulatory particle and uses the energy of ATP hydrolysis to unfold ubiquitinated substrates and translocate them into the proteolytic core, the 20S core particle.

Each subunit contains conserved Walker A and B motifs and an intersubunit signaling interface that coordinates ATP binding and hydrolysis around the ring. Subunits also interact with non-ATPase subunits such as Rpn1, Rpn2, and others to form the base subcomplex of the 19S regulatory particle. The exact arrangement and stoichiometry can vary among species, but the six subunits are generally essential for base function.

Biogenesis involves dedicated assembly factors and chaperones that aid in coordinating the sequential incorporation of Rpt1-6 with non-ATPase subunits before docking onto the 20S core particle. The result is a lid-bearing 19S regulatory particle capped onto the 20S proteasome, forming the 26S proteasome that degrades ubiquitinated substrates.

ATP-driven conformational changes in the Rpt ring control gate opening of the 20S core particle and substrate engagement. In addition to their catalytic role, Rpt subunits participate in regulatory processes that modulate proteasome activity in response to cellular conditions, stress, and signaling pathways.

Mutations or dysregulation of Rpt subunits can impair proteasome function and proteostasis, contributing to diseases such as cancer and neurodegenerative disorders. Rpt1-Rpt6 are conserved across eukaryotes, underscoring their central role in maintaining cellular protein quality control.