6B20
Crystal structure of a complex between G protein beta gamma dimer and an inhibitory Nanobody regulator
Summary for 6B20
| Entry DOI | 10.2210/pdb6b20/pdb |
| Descriptor | Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(T) subunit gamma-T1, Nanobody against G protein beta gamma dimer, ... (6 entities in total) |
| Functional Keywords | beta propeller, g protein, g protein coupled receptor-signaling, signaling protein |
| Biological source | Bos taurus More |
| Total number of polymer chains | 6 |
| Total formula weight | 113232.44 |
| Authors | Gulati, S.,Kiser, P.D.,Palczewski, K. (deposition date: 2017-09-19, release date: 2018-05-30, Last modification date: 2024-10-16) |
| Primary citation | Gulati, S.,Jin, H.,Masuho, I.,Orban, T.,Cai, Y.,Pardon, E.,Martemyanov, K.A.,Kiser, P.D.,Stewart, P.L.,Ford, C.P.,Steyaert, J.,Palczewski, K. Targeting G protein-coupled receptor signaling at the G protein level with a selective nanobody inhibitor. Nat Commun, 9:1996-1996, 2018 Cited by PubMed Abstract: G protein-coupled receptors (GPCRs) activate heterotrimeric G proteins by mediating a GDP to GTP exchange in the Gα subunit. This leads to dissociation of the heterotrimer into Gα-GTP and Gβγ dimer. The Gα-GTP and Gβγ dimer each regulate a variety of downstream pathways to control various aspects of human physiology. Dysregulated Gβγ-signaling is a central element of various neurological and cancer-related anomalies. However, Gβγ also serves as a negative regulator of Gα that is essential for G protein inactivation, and thus has the potential for numerous side effects when targeted therapeutically. Here we report a llama-derived nanobody (Nb5) that binds tightly to the Gβγ dimer. Nb5 responds to all combinations of β-subtypes and γ-subtypes and competes with other Gβγ-regulatory proteins for a common binding site on the Gβγ dimer. Despite its inhibitory effect on Gβγ-mediated signaling, Nb5 has no effect on Gα-mediated and Gα-mediated signaling events in living cells. PubMed: 29777099DOI: 10.1038/s41467-018-04432-0 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.34 Å) |
Structure validation
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