Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	A novel fusion tool to enable G protein-coupled receptor structure determination.
Journal, issue, pages	Acta Crystallogr D Struct Biol, Year 2026
Publish date	Jun 1, 2026
Authors	Nita R Shah / Mathieu Oosterlaken / Claudine Bisson / Mattia Bertinelli / Alicia M Churchill-Angus / Andrew Hutchin / Jola Kopec / Vadim Kotov / Ciaran R McFarlane / Erika Griss Pascualli / Ana Pavic / Matthias Zebisch / Cédric Fiez-Vandal / Edoardo Fabini / Stéphanie Duclos /
PubMed Abstract	Structure determination of G protein-coupled receptors (GPCRs) plays an important role in accelerating drug development against this medically important protein family. This study outlines the ...Structure determination of G protein-coupled receptors (GPCRs) plays an important role in accelerating drug development against this medically important protein family. This study outlines the development of a new fusion tool to enable structure determination of GPCRs in inactive conformations by cryo-EM. Initially, a PDB mining approach was applied to select eight naturally occurring proteins with the intention of fusing them into the intracellular loop 3 (ICL3) of GPCRs to create a suitable fiducial marker for cryo-EM workflows. During the selection process, candidates with known high-affinity protein binders were prioritized to enable a further increase in the protein mass of the fiducial marker. Fusion constructs were generated with adenosine receptor A (AR) and were assessed for expression and aggregation levels. For the two best-performing new fusion constructs, ligand binding was characterized to ensure that the fusion tag did not significantly affect protein behaviour. AR with a β-lactamase fusion in ICL3 and binding partner β-lactamase inhibitory protein II (BLIPII) was then selected to solve an antagonist-bound structure. The overall map was resolved to an average of 3.2 Å resolution with continuous helices connecting the β-lactamase to helices 5 and 6 of AR. Focused refinement of the AR region improved the local resolution and map detail in the orthosteric site, thereby allowing confident modelling of the antagonist ligand, ZM241385, which matches previously described X-ray crystallographic structures. This new fusion provides an alternative option for GPCR structure determination, with several potential benefits compared with existing tools, such as a more favourable position relative to the GPCR to reduce potential clashes.
External links	Acta Crystallogr D Struct Biol / PubMed:42138221
Methods	EM (single particle)
Resolution	2.77 - 3.43 Å
Structure data	55723 9t9p EMDB-55723, PDB-9t9p: Adenosine receptor A2a (A2AR)-beta-lactamase fusion bound to beta-lactamase inhibitory protein II (BLIPII) and ZM241385 Method: EM (single particle) / Resolution: 3.0 Å EMDB-56449: Consensus map of A2AR-beta-lactamase fusion + BLIPII Method: EM (single particle) / Resolution: 3.22 Å EMDB-56450: Focused map on beta-lactamase + BLIPII region Method: EM (single particle) / Resolution: 2.77 Å EMDB-56451: A2AR-focused map, with ligand ZM241385 Method: EM (single particle) / Resolution: 3.43 Å
Chemicals	ChemComp-ZMA: 4-{2-[(7-amino-2-furan-2-yl[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl)amino]ethyl}phenol / antagonist*YM
Source	other entries (others) streptomyces exfoliatus (bacteria) homo sapiens (human) bacillus licheniformis (bacteria) aequorea victoria (jellyfish)
Keywords	MEMBRANE PROTEIN / G-protein coupled receptor / GPCR / fusion tag