Structural Biochemistry/Membrane Proteins/Symporters

Symporters
Symporters is an indirect active transport. It couples the thermodynamically unfavorable flow of one species of ion or molecule up a concentration gradient with the favorable flow of a different species down a concentration gradient. In symporters, ions and/or molecules move in the same direction. Lastly, symporters can also be classified under secondary transporters or cotransporters because by definition they are membrane proteins that pump ions or molecules ‘uphill.’

Examples
Lactose Permease

This symporter uses H+ gradient across the E. coli membrane (outside H+ has higher concentration) generated by the oxidation of fuel molecules to drive the uptake of lactose and other sugars against a concentration gradient.

SGLT1 From the intestinal epithelium, SGLT1 transports sodium ions and glucose across the luminal membrane of the epithelial cells to be absorbed in the blood stream. This is the basis of oral rehydration therapy. Without this symporter, individual sodium channels and glucose uniports wouldn't be able to transfer glucose against the concentration gradient and into the bloodstream. Na+/K+-ATPase Na+,K+,2Cl- symporter Found in the loop of Henle in the renal tubules of the kidney, Na+,K+,2Cl- symporter transports these four molecules. Loop diuretics act on this protein.

Mechanism
The structure of lactose permease has been determined. The structure consists of two halves, each of which comprises six membrane - spanning alpha helices. Some of these helices are somewhat irregular. The two halves are well separated and are joined by a single stretch of polypeptide. In this structure, the sugar lies in a pocket in the center of the protein and is accessible from a path that leads from the interior of the cell. On the basis of these structures, a mechanism for symporter action has been developed (See Figure Below).

1. The cycle begins with the two halves oriented so that the opening to the binding pocket faces the outside of the cell. A proton from outside the cell binds to a residue in the permease.

2. In the protonated form, the permease binds lactose from outside the cell.

3. The structure everts to the form observed in the crystal structure.

4. Lactose is released to the inside of the cell by the permease.

5. A proton is released to the inside of the cell by the permease.

6. The permease everts to complete the cycle.

The site of protonation likely changes in the course of this cyle.