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| Title | Structures of distinct human acetylcholinesterase tetramer forms in complex with synaptic anchoring proteins. |
|---|---|
| Journal, issue, pages | Structure, Year 2026 |
| Publish date | Sep 22, 2026 |
 Authors | Jonah Cheung / Akira Karasawa /  |
| PubMed Abstract | Acetylcholinesterase (AChE) hydrolyzes the neurotransmitter acetylcholine in the nervous system. Higher order oligomeric forms of AChE are specific to synapses in vertebrates. The enzyme is anchored ...Acetylcholinesterase (AChE) hydrolyzes the neurotransmitter acetylcholine in the nervous system. Higher order oligomeric forms of AChE are specific to synapses in vertebrates. The enzyme is anchored to the basal lamina at neuromuscular junctions by ColQ and to neuronal membranes in the brain by the membrane protein PRiMA. We use cryo-electron microscopy to show that human AChE (hAChE) forms distinct tetramers in complex with the two synaptic anchors. The ColQ complex is more compact and square-like while the PRiMA complex is more open, asymmetric, and flexible. 3D variability analysis also reveals different flexibilities within the complexes, which are also different than AChE tetramers from other species. Binding of hAChE to the anchors occurs through a conserved mechanism but differences within the anchor sequences may lead to significantly different structures. Flexibility of hAChE tetramer form may be important for interactions with endogenous proteins in the nervous system. |
 External links | Structure / PubMed:42772275 |
| Methods | EM (single particle) |
| Resolution | 2.7 - 2.95 Å |
| Structure data |  EMDB-76967: Focus map for tetramerization domain of cryo-EM structure of an intact human acetylcholinesterase (T-form) tetramer in complex with ColQ  EMDB-76969: Focus map for catalytic domains A and B for cryo-EM structure of an intact human acetylcholinesterase (T-form) tetramer in complex with ColQ  EMDB-76970: Consensus map for cryo-EM structure of an intact human acetylcholinesterase (T-form) tetramer in complex with ColQ EMDB-76971, PDB-13co:  EMDB-76972: Focus map (C and D chains) for cryo-EM structure of an intact human acetylcholinesterase (T-form) tetramer in complex with PRiMA  EMDB-76973: Focus map (A and B chains) for cryo-EM structure of an intact human acetylcholinesterase (T-form) tetramer in complex with PRiMA  EMDB-76974: Consensus map for cryo-EM structure of an intact human acetylcholinesterase (T-form) tetramer in complex with PRiMA EMDB-76975, PDB-13cp: |
| Chemicals |  ChemComp-NAG: |
| Source |
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 Keywords | HYDROLASE |
homo sapiens (human)