This is a default text for your page Rhea Sachin Raodeo/Sandbox 1. Click above on edit this page to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia [1] or to the article describing Jmol [2] to the rescue.
Function
9W1N captures SLC37A4 in its lumen-facing, substrate-free conformation, representing the starting point of the G6P/Pi exchange cycle.
The central cavity is open toward the ER lumen and sealed on the cytosolic side, consistent with a transporter ready to release Pi or to bind luminal factors.
This state provides the template for how the transporter organises a pre-formed phosphate pocket before substrate binds.
Disease
9W1N reveals the positions of conserved Lys/His residues (K29, K64, H366) forming the phosphate-binding hotspot; many GSD-Ib mutations map directly onto this region.
The apo structure reveals how even small perturbations of the substrate cavity or cytoplasmic gate can disrupt the correct lumen-open geometry, explaining loss-of-function phenotypes.
Several pathogenic variants cluster at the dimer interface surfaces, clearly visualised in 9W1N.
Relevance
9W1N is the reference architecture for all other SLC37A4 structures, Pi-bound (9W1O), G6P-bound (9W1P), lateral dimers, and the inhibitor-bound cytosol-open state (9W1R).
It defines the resting, lumen-open gate essential for understanding:
How substrates gain access to the ER-facing cavity
How is antiport asymmetry maintained
Which structural elements move during transport
Serves as a baseline for comparing disease mutations, substrate recognition, and inhibitor locking.
Structural highlights
State captured: Apo, lumen-facing, antiparallel dimer (C2 symmetry).
Resolution: ~3.2 Å cryo-EM, allowing accurate visualisation of the central cavity, gates, and conserved charged residues.
Dimer architecture:
Unique antiparallel packing of the two protomers.
The interface is tight but still allows for large-scale rearrangements, as seen in lateral dimers.
Cavity features:
A positively charged, pre-shaped phosphate pocket despite the absence of a ligand.
The residues K29, K64, M145, and H366 are positioned for immediate substrate coordination.
Gating:
Cytosolic gate closed—TM helices pack to block access.
The luminal gate is open, showing a clear solvent-accessible path.
Mechanistic role:
This represents the lumen-access state in the alternating-access cycle.
It serves as the structural endpoint opposite the cytosol-open inhibitor-bound structure (9W1R).
This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
