Sandbox 9CC8 AA: Difference between revisions

The cryo-EM structure of the resistosome reveals that six identical NRC4 protomers assemble into a <scene name='10/1095719/Symmetric_hexamer/1'>symmetric hexamer</scene> of ~180Å in diameter at the plasma membrane. <scene name='10/1095719/Single_protomer/1'>Each protomer</scene> contains a leucine-rich repeat (LRR) domain and a nucleotide-binding (NB-ARC) domain, which is itself subdivided into the Nucleotide-Binding domain (NBD), Helical Domain 1 (HD1), and a Winged-Helix Domain (WHD). The coiled-coil (CC) domains of each protomer face inward, enabling formation of a <scene name='10/1095719/Central_pore/2'>central pore</scene>, which is crucial for calcium (Ca²⁺) influx. Stability between adjacent CC domains is achieved when the α2-helix from one protomer engages with the α3-helix of its neighboring protomer. This pore is lined by the <scene name='10/1095719/Alpha_1_helix/3'>N-terminal</scene> α1-helix from each of the six protomers and is rich in <scene name='10/1095719/Acidic_pore_lining/1'>key acidic residues</scene>, creating the Ca²⁺ channel. Crucially, the nucleotide-binding pocket of the active hexamer is occupied by <scene name='10/1095719/Nucleotide_binding_pocket/1'>ATP</scene> and Mg²⁺. This ATP binding is the essential trigger for oligomerization, locking the complex into its active, channel-forming state. Structural analyses uncovered two states of the complex: the active hexamer (9CC8) and an alternative inactive <scene name='10/1095719/Dodecamer/1'>(9CC9) dodecameric</scene> 'dumbbell' form where the CC domains of one ring are shielded by the LRR domains of the other, and the pore is closed.