8SJX
Structure of lens aquaporin-0 array in sphingomyelin/cholesterol bilayer (2SM:1Chol)
Summary for 8SJX
| Entry DOI | 10.2210/pdb8sjx/pdb |
| Descriptor | Lens fiber major intrinsic protein, [(E,2S,3R)-2-(hexadecanoylamino)-3-oxidanyl-octadec-4-enyl] 2-(trimethylazaniumyl)ethyl phosphate, CHOLESTEROL, ... (4 entities in total) |
| Functional Keywords | aquaporin, lens, cholesterol, lipid raft, membrane protein |
| Biological source | Ovis aries (sheep) |
| Total number of polymer chains | 1 |
| Total formula weight | 33592.74 |
| Authors | Chiu, P.-L.,Walz, T. (deposition date: 2023-04-18, release date: 2024-04-24, Last modification date: 2024-11-13) |
| Primary citation | Chiu, P.L.,Orjuela, J.D.,de Groot, B.L.,Aponte Santamaria, C.,Walz, T. Structure and dynamics of cholesterol-mediated aquaporin-0 arrays and implications for lipid rafts. Elife, 12:-, 2024 Cited by PubMed Abstract: Aquaporin-0 (AQP0) tetramers form square arrays in lens membranes through a yet unknown mechanism, but lens membranes are enriched in sphingomyelin and cholesterol. Here, we determined electron crystallographic structures of AQP0 in sphingomyelin/cholesterol membranes and performed molecular dynamics (MD) simulations to establish that the observed cholesterol positions represent those seen around an isolated AQP0 tetramer and that the AQP0 tetramer largely defines the location and orientation of most of its associated cholesterol molecules. At a high concentration, cholesterol increases the hydrophobic thickness of the annular lipid shell around AQP0 tetramers, which may thus cluster to mitigate the resulting hydrophobic mismatch. Moreover, neighboring AQP0 tetramers sandwich a cholesterol deep in the center of the membrane. MD simulations show that the association of two AQP0 tetramers is necessary to maintain the deep cholesterol in its position and that the deep cholesterol increases the force required to laterally detach two AQP0 tetramers, not only due to protein-protein contacts but also due to increased lipid-protein complementarity. Since each tetramer interacts with four such 'glue' cholesterols, avidity effects may stabilize larger arrays. The principles proposed to drive AQP0 array formation could also underlie protein clustering in lipid rafts. PubMed: 39222068DOI: 10.7554/eLife.90851 PDB entries with the same primary citation |
| Experimental method | ELECTRON CRYSTALLOGRAPHY (2.5 Å) |
Structure validation
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