8BHF
Cryo-EM structure of stalled rabbit 80S ribosomes in complex with human CCR4-NOT and CNOT4
This is a non-PDB format compatible entry.
Summary for 8BHF
| Entry DOI | 10.2210/pdb8bhf/pdb |
| EMDB information | 16052 |
| Descriptor | Ribosomal protein L15, TRASH domain-containing protein, Ribosomal protein L23/L25 N-terminal domain-containing protein, ... (88 entities in total) |
| Functional Keywords | translational control, mrna decay, deadenylation, ribosome stalling, human ccr4-not, ribosome |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 86 |
| Total formula weight | 3706651.19 |
| Authors | Absmeier, E.,Chandrasekaran, V.,O'Reilly, F.J.,Stowell, J.A.W.,Rappsilber, J.,Passmore, L.A. (deposition date: 2022-10-31, release date: 2023-09-06, Last modification date: 2024-11-13) |
| Primary citation | Gangwar, S.P.,Yen, L.Y.,Yelshanskaya, M.V.,Korman, A.,Jones, D.R.,Sobolevsky, A.I. Modulation of GluA2-gamma 5 synaptic complex desensitization, polyamine block and antiepileptic perampanel inhibition by auxiliary subunit cornichon-2. Nat.Struct.Mol.Biol., 30:1481-1494, 2023 Cited by PubMed Abstract: Synaptic complexes of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs) with auxiliary subunits mediate most excitatory neurotransmission and can be targeted to treat neuropsychiatric and neurological disorders, including epilepsy. Here we present cryogenic-electron microscopy structures of rat GluA2 AMPAR complexes with inhibitory mouse γ5 and potentiating human cornichon-2 (CNIH2) auxiliary subunits. CNIH2 appears to destabilize the desensitized state of the complex by reducing the separation of the upper lobes in ligand-binding domain dimers. At the same time, CNIH2 stabilizes binding of polyamine spermidine to the selectivity filter of the closed ion channel. Nevertheless, CNIH2, and to a lesser extent γ5, attenuate polyamine block of the open channel and reduce the potency of the antiepileptic drug perampanel that inhibits the synaptic complex allosterically by binding to sites in the ion channel extracellular collar. These findings illustrate the fine-tuning of synaptic complex structure and function in an auxiliary subunit-dependent manner, which is critical for the study of brain region-specific neurotransmission and design of therapeutics for disease treatment. PubMed: 37653241DOI: 10.1038/s41594-023-01080-x PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.1 Å) |
Structure validation
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