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 N-terminal α1-helix from each of the six protomers and is rich in key acidic residues, creating the Ca²⁺ channel. While ATP binding initiates assembly, the final resolved cryo-EM structure (9CC8) represents the post-hydrolysis state, with ADP and Mg²⁺ bound, and inter-subunit contacts stabilizing the overall complex. Structural analyses uncovered two states of the complex: the active hexamer (9CC8) and an alternative inactive (9CC9) dodecameric 'dumbbell' form where the CC domains of one ring are shielded by the LRR domains of the other, and the pore is closed.