Title : A substrate access tunnel in the cytosolic
domain is not an essential feature of the solute carrier 4 (SLC4) family of bicarbonate transporters
Abstract :
- Anion exchanger 1 (AE1; Band 3 ; SLC4A1 ) is the founding member of the solute carrier 4 (SLC4) family of bicarbonate transporters that includes chloride/bicarbonate AEs and Na(+)-bicarbonate co-transporters (NBCs)
- These membrane proteins consist of an amino-terminal cytosolic domain involved in protein interactions and a carboxyl-terminal membrane domain that carries out the transport function
- Mutation of a conserved arginine residue (R298S) in the cytosolic domain of NBCe1 ( SLC4A4 ) is linked to proximal renal tubular acidosis and results in impaired transport function, suggesting that the cytosolic domain plays a role in substrate permeation
- Introduction of single and double mutations at the equivalent arginine ( Arg(283) ) and at an interacting glutamate ( Glu(85) ) in the cytosolic domain of human AE1 ( cdAE1 ) had no effect on the cell surface expression or the transport activity of AE1 expressed in HEK-293 cells
- In addition, the membrane domain of AE1 ( mdAE1 ) efficiently mediated anion transport
- A 2.1-Å resolution crystal structure of cdΔ54 AE1 ( residues 55-356 of cdAE1 ) lacking the amino-terminal and carboxyl-terminal disordered regions , produced at physiological pH, revealed an extensive hydrogen-bonded network involving Arg(283) and Glu(85)
- Mutations at these residues affected the pH-dependent conformational changes and stability of cdΔ54 AE1
- As these structural alterations did not impair functional expression of AE1 , the cytosolic and membrane domains operate independently
- A substrate access tunnel within the cytosolic domain is not present in AE1 and therefore is not an essential feature of the SLC4 family of bicarbonate transporters
Output (sent_index, trigger,
protein,
sugar,
site):
Output(Part-Of) (sent_index,
protein,
site):
- 3. NBCe1, domain
- 4. AE1, domain
- 5. AE1, domain
- 6. cdAE1, residues 55-356
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):