13.5 : ATP Driven Pumps I: An Overview

ATP-driven pumps, also known as transport ATPases, are integral membrane proteins. They have binding sites for ATP located on the membrane's cytosolic side and the ion-conducting domain in the transmembrane region. These pumps use the free energy released from ATP hydrolysis to move the solutes across cell membranes against an electrochemical gradient.

There are four main types of ATP-driven pumps - P-type, V-type, F-type, and ABC transporter. All these pumps are of varying complexities and are usually multisubunit structures. They employ two very different mechanisms: an elaborate rotary mechanism, used by F-and V-type pumps, and a simpler alternating access mechanism (or inward-facing to outward-facing conformational change) as seen in ABC transporters and P-type pumps.

P-type pumps contain a transmembrane catalytic α subunit, which is a smaller β subunit, with regulatory functions and three cytosolic domains. Many of these pumps are tetramers composed of two copies each of the α and β subunits. ATP hydrolysis phosphorylates one of the cytosolic domains, hence the name P-type, allowing the solutes to move to the other side of the membrane.

V-type pumps are multisubunit and contain at least five transmembrane proteins and eight types of extrinsic polypeptides that form the cytosolic domain. They couple ATP hydrolysis to transport protons against a concentration gradient.

The F-type pumps or ATP synthases are a class of transporters that function as reverse proton pumps. The energy released by the protons' movement down the electrochemical gradient is used to power the energetically unfavorable ATP synthesis. However, these transporters can also work in the reverse direction in some bacteria, where they hydrolyze ATP to drive protons across the membrane.

A defect in the genes that encode for these pumps' normal functioning could lead to various disorders. For example, a defect in the copper-transporting P-type pumps leads to the accumulation of copper in the brain and liver, a condition called Wilson's disease. Similarly, mutations in one of the V-type pump subunits are the primary cause of osteopetrosis. Additionally, different types of renal tubular acidosis are caused by defects in the V-type pumps' activity.

On the other hand, ABC transporters form the largest family of membrane transporters. They are well known for exporting drugs in bacterial and mammalian cells, leading to drug resistance.