6DJB
Structure of human Volume Regulated Anion Channel composed of SWELL1 (LRRC8A)
Summary for 6DJB
| Entry DOI | 10.2210/pdb6djb/pdb |
| EMDB information | 7935 |
| Descriptor | Volume-regulated anion channel subunit LRRC8A (1 entity in total) |
| Functional Keywords | anion channel, lrrc8a, swell1, membrane protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 6 |
| Total formula weight | 565911.10 |
| Authors | Kefauver, J.M.,Saotome, K.,Pallesen, J.,Cottrell, C.A.,Ward, A.B.,Patapoutian, A. (deposition date: 2018-05-24, release date: 2018-08-15, Last modification date: 2024-10-23) |
| Primary citation | Kefauver, J.M.,Saotome, K.,Dubin, A.E.,Pallesen, J.,Cottrell, C.A.,Cahalan, S.M.,Qiu, Z.,Hong, G.,Crowley, C.S.,Whitwam, T.,Lee, W.H.,Ward, A.B.,Patapoutian, A. Structure of the human volume regulated anion channel. Elife, 7:-, 2018 Cited by PubMed Abstract: SWELL1 (LRRC8A) is the only essential subunit of the Volume Regulated Anion Channel (VRAC), which regulates cellular volume homeostasis and is activated by hypotonic solutions. SWELL1, together with four other LRRC8 family members, potentially forms a vastly heterogeneous cohort of VRAC channels with different properties; however, SWELL1 alone is also functional. Here, we report a high-resolution cryo-electron microscopy structure of full-length human homo-hexameric SWELL1. The structure reveals a trimer of dimers assembly with symmetry mismatch between the pore-forming domain and the cytosolic leucine-rich repeat (LRR) domains. Importantly, mutational analysis demonstrates that a charged residue at the narrowest constriction of the homomeric channel is an important pore determinant of heteromeric VRAC. Additionally, a mutation in the flexible N-terminal portion of SWELL1 affects pore properties, suggesting a putative link between intracellular structures and channel regulation. This structure provides a scaffold for further dissecting the heterogeneity and mechanism of activation of VRAC. PubMed: 30095067DOI: 10.7554/eLife.38461 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.4 Å) |
Structure validation
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