The dimerized pentraxin-like domain of the adhesion G protein-coupled receptor 112 (ADGRG4) suggests function in sensing mechanical forces.

Autor:	Kieslich B; Institute of Bioanalytical Chemistry, Center for Biotechnology and Biomedicine, Leipzig University, Leipzig, Germany; Rudolf Schönheimer Institute of Biochemistry, Medical Faculty, Leipzig University, Leipzig, Germany. Electronic address: bjoern.kieslich@bbz.uni-leipzig.de., Weiße RH; Institute of Bioanalytical Chemistry, Center for Biotechnology and Biomedicine, Leipzig University, Leipzig, Germany., Brendler J; Institute of Anatomy, Medical Faculty, Leipzig University, Leipzig, Germany., Ricken A; Institute of Anatomy, Medical Faculty, Leipzig University, Leipzig, Germany., Schöneberg T; Rudolf Schönheimer Institute of Biochemistry, Medical Faculty, Leipzig University, Leipzig, Germany. Electronic address: schoberg@medizin.uni-leipzig.de., Sträter N; Institute of Bioanalytical Chemistry, Center for Biotechnology and Biomedicine, Leipzig University, Leipzig, Germany. Electronic address: strater@bbz.uni-leipzig.de.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2023 Dec; Vol. 299 (12), pp. 105356. Date of Electronic Publication: 2023 Oct 18.
DOI:	10.1016/j.jbc.2023.105356
Abstrakt:	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 2+ -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. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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