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 Gαi 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. Here, we show that all RZ subfamily members have similar and relatively low GAP activity towards Gαo. We characterized four RZ-specific structural motifs that mediate this low activity, and suggest they perturb optimal interactions with the Gα subunit. Indeed, inserting these RZ-specific motifs into the representative high-activity RGS16 impaired GAP activity in a non-additive manner. Our results provide residue-level insights into the specificity determinants of the RZ subfamily, and enable to study their interactions in signaling cascades by using redesigned mutants such as those presented in this work.
|Number of pages||6|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - 18 Sep 2018|
Bibliographical noteFunding Information:
This work was supported by Israel Science Foundation grants: 1454/13 , 1959/13 , 2155/15 .
© 2018 Elsevier Inc.
- G protein signaling
- Interaction specificity
- Protein structure
- RGS proteins
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology