Structural motifs in the RGS RZ subfamily combine to attenuate interactions with Gα subunits.

Regulators of G-protein Signaling (RGS) proteins inactivate heterotrimeric G proteins, thereby setting the duration of active signaling. In particular, the RGS RZ subfamily, which consists of RGS17, RGS19, and RGS20, mediates numerous physiological functions and human pathologies - mostly by functioning as GTPase Activating Proteins (GAPs) towards the Gα subfamily. Yet, which RZ subfamily members mediate particular functions and how their GAP activity and specificity are governed at the amino acid level is not well understood.