6CB8
Cryo-EM structure of the Gasdermin A3 membrane pore
Summary for 6CB8
| Entry DOI | 10.2210/pdb6cb8/pdb |
| EMDB information | 7449 |
| Descriptor | Gasdermin-A3, CARDIOLIPIN (2 entities in total) |
| Functional Keywords | pyroptosis, pore forming protein, immune system |
| Biological source | Mus musculus (Mouse) |
| Total number of polymer chains | 1 |
| Total formula weight | 31865.08 |
| Authors | |
| Primary citation | Ruan, J.,Xia, S.,Liu, X.,Lieberman, J.,Wu, H. Cryo-EM structure of the gasdermin A3 membrane pore. Nature, 557:62-67, 2018 Cited by PubMed Abstract: Gasdermins mediate inflammatory cell death after cleavage by caspases or other, unknown enzymes. The cleaved N-terminal fragments bind to acidic membrane lipids to form pores, but the mechanism of pore formation remains unresolved. Here we present the cryo-electron microscopy structures of the 27-fold and 28-fold single-ring pores formed by the N-terminal fragment of mouse GSDMA3 (GSDMA3-NT) at 3.8 and 4.2 Å resolutions, and of a double-ring pore at 4.6 Å resolution. In the 27-fold pore, a 108-stranded anti-parallel β-barrel is formed by two β-hairpins from each subunit capped by a globular domain. We identify a positively charged helix that interacts with the acidic lipid cardiolipin. GSDMA3-NT undergoes radical conformational changes upon membrane insertion to form long, membrane-spanning β-strands. We also observe an unexpected additional symmetric ring of GSDMA3-NT subunits that does not insert into the membrane in the double-ring pore, which may represent a pre-pore state of GSDMA3-NT. These structures provide a basis that explains the activities of several mutant gasdermins, including defective mutants that are associated with cancer. PubMed: 29695864DOI: 10.1038/s41586-018-0058-6 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.8 Å) |
Structure validation
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