6b20

From Proteopedia

Jump to: navigation, search

Crystal structure of a complex between G protein beta gamma dimer and an inhibitory Nanobody regulator

Structural highlights

6b20 is a 6 chain structure with sequence from Bos taurus and Lama glama. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.34Å
Ligands:CL
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GBG1_BOVIN Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.

Publication Abstract from PubMed

G protein-coupled receptors (GPCRs) activate heterotrimeric G proteins by mediating a GDP to GTP exchange in the Galpha subunit. This leads to dissociation of the heterotrimer into Galpha-GTP and Gbetagamma dimer. The Galpha-GTP and Gbetagamma dimer each regulate a variety of downstream pathways to control various aspects of human physiology. Dysregulated Gbetagamma-signaling is a central element of various neurological and cancer-related anomalies. However, Gbetagamma also serves as a negative regulator of Galpha 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 Gbetagamma dimer. Nb5 responds to all combinations of beta-subtypes and gamma-subtypes and competes with other Gbetagamma-regulatory proteins for a common binding site on the Gbetagamma dimer. Despite its inhibitory effect on Gbetagamma-mediated signaling, Nb5 has no effect on Galphaq-mediated and Galphas-mediated signaling events in living cells.

Targeting G protein-coupled receptor signaling at the G protein level with a selective nanobody inhibitor.,Gulati S, Jin H, Masuho I, Orban T, Cai Y, Pardon E, Martemyanov KA, Kiser PD, Stewart PL, Ford CP, Steyaert J, Palczewski K Nat Commun. 2018 May 18;9(1):1996. doi: 10.1038/s41467-018-04432-0. PMID:29777099[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Loading citation details..
No citations found

See Also

References

  1. Gulati S, Jin H, Masuho I, Orban T, Cai Y, Pardon E, Martemyanov KA, Kiser PD, Stewart PL, Ford CP, Steyaert J, Palczewski K. Targeting G protein-coupled receptor signaling at the G protein level with a selective nanobody inhibitor. Nat Commun. 2018 May 18;9(1):1996. doi: 10.1038/s41467-018-04432-0. PMID:29777099 doi:http://dx.doi.org/10.1038/s41467-018-04432-0

Contents


PDB ID 6b20

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools