Structural basis for adhesion G protein-coupled receptor Gpr126 function.
Demet Araç group (University of Chicago) and collaborators
The group of Demet Araç and collaborators determined
the x-ray crystal structure of the full-length extracellular region of
Gpr126, an adhesion G-protein coupled receptor with essential roles in
axon myelination, ear development, and heart development. The structure
revealed an interesting architecture of this region that is important
for its function, and they also found that different forms of Gpr126
can adopt different architectures to possibly carry out different
functions. The structure also helped in identifying a key functional
site on the protein, which led to many defects when mutated in
zebrafish. These results demonstrate that Gpr126 utilizes a
multi-faceted dynamic approach to regulate receptor function and
provide relevant insights for drug design against Gpr126 and other
adhesion G-protein coupled receptors.
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Figure: (center) Crystal
structure of the full extracellular region of zebrafish Gpr126, colored
by domain (dark blue: CUB, cyan: PTX, green: SEA, yellow: HormR, red:
GAIN). (left) Conserved calcium-binding site within CUB domain mediates
interdomain interactions and is an important functional site. (right)
Conserved disulfide-stabilized loop contributes to the stabilization of
the closed conformation. |
Citation: Leon, K, Cunningham, RL, Riback, JA,
Feldman, E, Li, J, Sosnick, TR, Zhao, M, Monk, KR, Araç, D.,
Structural basis for adhesion G protein-coupled receptor Gpr126
function, Nat.Commun. 11:194 (2020). DOI:
10.1038/s41467-019-14040-1
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