4U15: M3-mT4L receptor bound to tiotropium

G protein-coupled receptors (GPCRs) mediate the majority of cellular responses to hormones and neurotransmitters. Most GPCR crystal structures have been obtained using a fusion protein strategy where the flexible third intracellular loop is replaced by T4 lysozyme (T4L). However, wild-type T4L may not be ideally suited for all GPCRs because of its size and the inherent flexibility between the N- and C-terminal subdomains. Here we report two modified T4L variants, designed to address flexibility and size, that can be used to optimize crystal quality or promote alternative packing interactions. These variants were tested on the M3 muscarinic receptor (M3). The original M3-T4L fusion protein produced twinned crystals that yielded a 3.4 A structure from a 70 crystal data set. We replaced T4L with the modified T4L variants. Both T4L variants yielded M3 muscarinic receptor crystals with alternate lattices that were not twinned, including one that was solved at 2.8 A resolution.
PDB ID: 4U15Download
MMDB ID: 125113
PDB Deposition Date: 2014/7/15
Updated in MMDB: 2017/12
Experimental Method:
x-ray diffraction
Resolution: 2.8  Å
Source Organism:
Similar Structures:
Biological Unit for 4U15: monomeric; determined by author
Molecular Components in 4U15
Label Count Molecule
Protein (1 molecule)
Muscarinic Acetylcholine Receptor M3,lysozyme,muscarinic Acetylcholine Receptor M3(Gene symbol: Chrm3)
Molecule annotation
Chemicals (6 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB