8B55

Human ADGRG4 PTX-like domain

8B55 の概要

• エントリーDOI: 10.2210/pdb8b55/pdb
• 分子名称: Adhesion G-protein coupled receptor G4, MAGNESIUM ION (3 entities in total)
• 機能のキーワード: adhesion gpcr, extracellular region, n-terminus, signaling protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 27469.47

構造登録者

Kieslich, B.,Straeter, N. (登録日: 2022-09-21, 公開日: 2022-10-19, 最終更新日: 2024-11-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.36 Å)