6AM3
Regulator of G protein signaling (RGS) 17 in complex with Ca2+
Summary for 6AM3
| Entry DOI | 10.2210/pdb6am3/pdb |
| Descriptor | Regulator of G-protein signaling 17, CALCIUM ION, TETRAETHYLENE GLYCOL, ... (5 entities in total) |
| Functional Keywords | g protein, regulator, signaling, signaling protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 33209.78 |
| Authors | Sieng, M.,Lyon, A.M. (deposition date: 2017-08-09, release date: 2019-02-13, Last modification date: 2023-10-04) |
| Primary citation | Sieng, M.,Hayes, M.P.,O'Brien, J.B.,Andrew Fowler, C.,Houtman, J.C.,Roman, D.L.,Lyon, A.M. High-resolution structure of RGS17 suggests a role for Ca2+in promoting the GTPase-activating protein activity by RZ subfamily members. J.Biol.Chem., 294:8148-8160, 2019 Cited by PubMed Abstract: Regulator of G protein signaling (RGS) proteins are negative regulators of G protein-coupled receptor (GPCR) signaling through their ability to act as GTPase-activating proteins (GAPs) for activated Gα subunits. Members of the RZ subfamily of RGS proteins bind to activated Gα, Gα, and Gα proteins in the nervous system and thereby inhibit downstream pathways, including those involved in Ca-dependent signaling. In contrast to other RGS proteins, little is known about RZ subfamily structure and regulation. Herein, we present the 1.5-Å crystal structure of RGS17, the most complete and highest-resolution structure of an RZ subfamily member to date. RGS17 cocrystallized with Ca bound to conserved positions on the predicted Gα-binding surface of the protein. Using NMR chemical shift perturbations, we confirmed that Ca binds in solution to the same site. Furthermore, RGS17 had greater than 55-fold higher affinity for Ca than for Mg Finally, we found that Ca promotes interactions between RGS17 and activated Gα and decreases the for GTP hydrolysis, potentially by altering the binding mechanism between these proteins. Taken together, these findings suggest that Ca positively regulates RGS17, which may represent a general mechanism by which increased Ca concentration promotes the GAP activity of the RZ subfamily, leading to RZ-mediated inhibition of Ca signaling. PubMed: 30940727DOI: 10.1074/jbc.RA118.006059 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.53 Å) |
Structure validation
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