%0 Journal Article
%A Kondo, Yasushi
%A Hatton, Caitlin
%A Cheng, Robert
%A Trabuco, Matilde
%A Glover, Hannah
%A Bertrand, Quentin
%A Stierli, Fabienne
%A Seidel, Hans-Peter
%A Mason, Thomas
%A Sarma, Sivathmika
%A Tellkamp, Friedjof
%A Kepa, Michal
%A Dworkowski, Florian
%A Mehrabi, Pedram
%A Hennig, Michael
%A Standfuss, Joerg
%T Apo‐state structure of the metabotropic glutamate receptor 5 transmembrane domain obtained using a photoswitchable ligand
%J Protein science
%V 34
%N 7
%@ 0961-8368
%C Hoboken, NJ
%I Wiley
%M PUBDB-2025-02316
%P e70104
%D 2025
%X Metabotropic glutamate receptor 5 (mGlu5) is implicated in various neurodegenerative disorders, making it an attractive drug target. Although several ligand-bound crystal structures of mGlu5 exist, their apo-state crystal structure remains unknown. Here, we study mGlu5 structural changes using the photochemical affinity switch, alloswitch-1, in combination with time-resolved freeze-trapping methods. By X-ray crystallography, we demonstrated that isomerizing alloswitch-1 leads to its release from the binding pocket within a few seconds. The apo structure, determined at a resolution of 2.9 Å, is more comparable to the inactive state than to the active state. Our approach presents an accessible alternative to time-resolved serial crystallography for capturing thermodynamically stable transient intermediates. The mGlu5 apo-structure provides molecular insights into the ligand-free allosteric pocket, which can guide the design of new allosteric modulators.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40521617
%R 10.1002/pro.70104
%U https://bib-pubdb1.desy.de/record/632990