8B55

Human ADGRG4 PTX-like domain

Summary for 8B55

• Entry DOI: 10.2210/pdb8b55/pdb
• Descriptor: Adhesion G-protein coupled receptor G4, MAGNESIUM ION (3 entities in total)
• Functional Keywords: adhesion gpcr, extracellular region, n-terminus, signaling protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 27469.47

Authors

Kieslich, B.,Straeter, N. (deposition date: 2022-09-21, release date: 2022-10-19, Last modification date: 2024-11-20)

Primary citation

Kieslich, B.,Weisse, R.H.,Brendler, J.,Ricken, A.,Schoneberg, T.,Strater, N.
The dimerized pentraxin-like domain of the adhesion G protein-coupled receptor 112 (ADGRG4) suggests function in sensing mechanical forces.
J.Biol.Chem., 299:105356-105356, 2023

PubMed Abstract: Adhesion G protein-coupled receptors (aGPCRs) feature large extracellular regions with modular domains that often resemble protein classes of various function. The pentraxin (PTX) domain, which is predicted by sequence homology within the extracellular region of four different aGPCR members, is well known to form pentamers and other oligomers. Oligomerization of GPCRs is frequently reported and mainly driven by interactions of the seven-transmembrane region and N or C termini. While the functional importance of dimers is well-established for some class C GPCRs, relatively little is known about aGPCR multimerization. Here, we showcase the example of ADGRG4, an orphan aGPCR that possesses a PTX-like domain at its very N-terminal tip, followed by an extremely long stalk containing serine-threonine repeats. Using X-ray crystallography and biophysical methods, we determined the structure of this unusual PTX-like domain and provide experimental evidence for a homodimer equilibrium of this domain which is Ca-independent and driven by intermolecular contacts that differ vastly from the known soluble PTXs. The formation of this dimer seems to be conserved in mammalian ADGRG4 indicating functional relevance. Our data alongside of theoretical considerations lead to the hypothesis that ADGRG4 acts as an in vivo sensor for shear forces in enterochromaffin and Paneth cells of the small intestine.

PubMed: 37863265
DOI: 10.1016/j.jbc.2023.105356

Experimental method

X-RAY DIFFRACTION (1.36 Å)