User:Christopher Koehn/sandbox 1

From Proteopedia

Revision as of 02:21, 7 April 2010

Introduction to Sodium-Potassium-ATPases

The sodium-potassium-ATPase, also known as the Na⁺-K⁺ pump or the sodium pump, is the protein responsible for the ATP-dependent coupled transport of sodium and potassium ions across the plasma membrane. The Na⁺-K⁺ pump is found in all animal cells and is a major force in maintaining the concentration gradients of these ions across the membrane. These gradients provide energy for several cellular functions including control of membrane potential, cell size, and pH homeostasis, and nutrient uptake. Each cycle of ATP hydrolysis, the protein transports three Na⁺ ions out of the cell and two K⁺ ions across the plasma membrane into the cell. In addition to its role as a transport protein, the sodium-potassium-pump has also been shown to act as a receptor for cardiotonic steroid signalling. The sodium-potassium pump was first described in 1957 by Jens C. Skou and he was awarded the Nobel Prize in Chemistry in 1997 for this discovery.

Structure

()

The Na⁺-K⁺ pump is a P-type ATPase with a structure similar to the H⁺-K⁺-ATPase[1] and the sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA)[2]. Overall, the structure of the sodium-potassium-pump is a transmembrane protein with three subunits labeled α, β, and FXYD.

α-Subunit

The α-subunit is the largest subunit and contains the binding sites for Na⁺, K⁺, and ATP. This subunit is composed of 10 transmembrane α-helices (M1-M10). These helices are centered around a three helix bundle formed by M4-M6. The binding sites for K⁺ and Na⁺ are located within the transmembrane helices. Additionally, there are located on the cytoplasmic face of the membrane: the actuator domain (A), the nucleotide-binding domain (N), and the phosphorylation domain (P). There are 4 known isoforms of the α-subunit, but even the two most divergent isoforms share 78% sequence identity. The majority of structural diversity among the isoforms occurs at the N-terminus, the first extracellular loop, and the third cytosolic domain. This diversity can influence the rate ion transport and the ability to act as a signaling receptor.

β-Subunit

The β-subunit is a single spanning membrane protein with a transmembrane α-helix and a glycosylated extracellular domain. This subunit uses a to bind to the M7 and M10 helices of the α-subunit within the lipid bilayer. These residues also make contact with a cholesterol molecule, the presence of which is necessary for ion transport to occur. Contact between the α and β subunits also occurs at various residues in the extracellular domains. It has important roles in targeting the protein to the membrane and providing stability. It also has a role in providing binding specificity for potassium ions.

FXYD Subunit

The FXYD subunit, sometimes known as the γ-subunit, is an accessory regulatory protein comprised of a transmembrane α-helix and an extracellular domain (which is not shown in this structure). Regulation of ion pumping action by FXYD has been shown to be tissue and isoform specific.

References