8VVC
Cryo-EM structure of human ABC transporter (hABCC1) with nucleotide-binding domain 2
Summary for 8VVC
| Entry DOI | 10.2210/pdb8vvc/pdb |
| EMDB information | 43550 |
| Descriptor | Multidrug resistance-associated protein 1 (1 entity in total) |
| Functional Keywords | cgamp exporter, multidrug-resistant protein, abc transporter, membrane protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 171762.95 |
| Authors | Shinde, O.,Li, P. (deposition date: 2024-01-30, release date: 2024-12-25, Last modification date: 2025-01-29) |
| Primary citation | Shinde, O.,Boyer, J.A.,Cambier, S.,VanPortfliet, J.J.,Sui, X.,Yadav, G.P.,Viverette, E.G.,Borgnia, M.J.,West, A.P.,Zhang, Q.,Stetson, D.B.,Li, P. Structures of ATP-binding cassette transporter ABCC1 reveal the molecular basis of cyclic dinucleotide cGAMP export. Immunity, 58:59-73.e5, 2025 Cited by PubMed Abstract: Cyclic nucleotide GMP-AMP (cGAMP) plays a critical role in mediating the innate immune response through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. Recent studies showed that ATP-binding cassette subfamily C member 1 (ABCC1) is a cGAMP exporter. The exported cGAMP can be imported into uninfected cells to stimulate a STING-mediated innate immune response. However, the molecular basis of cGAMP export mediated by ABCC1 remains unclear. Here, we report the cryoelectron microscopy (cryo-EM) structures of human ABCC1 in a ligand-free state and a cGAMP-bound state. These structures reveal that ABCC1 forms a homodimer via its N-terminal transmembrane domain. The ligand-bound structure shows that cGAMP is recognized by a positively charged pocket. Mutagenesis and functional studies confirmed the roles of the ligand-binding pocket in cGAMP recognition and export. This study provides insights into the structure and function of ABCC1 as a cGAMP exporter and lays a foundation for future research targeting ABCC1 in infection and anti-cancer immunity. PubMed: 39765229DOI: 10.1016/j.immuni.2024.12.002 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.32 Å) |
Structure validation
Download full validation report
