1. MANHATTANVILLE COLLEGE
The Na+/K+ Pump
A Discussion of structural and functional
importance in the cell membrane
Stephen Corvini
11/30/2011
Dr. Bettica
Molecular Cell Biology
2. Molecular Cell Biology Final Paper S.Corvini 2011
Stephen Corvini
Molecular Cell Biology
Final Paper
Dr. Bettica
November 30, 2011
The sodium potassium pump resides as a core example of an ATP driven symport
channel protein that exists within the cell membrane. It is a primary transport sarcolemmal
transport protein that works to maintain the ion gradient between sodium and potassium ions
within the external and internal cellular environment (Smith and Crampin, 2004). As a member
of the integrin protein family this structure is rooted within the lipid bilayer and possesses a
multiple ligand-specific binding sites on both its external and internal regions (Puts and Holthuis,
2009). It is known as a P-pump because it is driven by the process of phosphorylation. Through
the addition and subtraction of phosphates from the protein conformational changes occur which
allow this structure to act as a multi-transport unit within the membrane (Smith and Crampin,
2009). This symport molecule is vital to a series of various cell functions.
Regarding the structure of the P-(Na+/K+) ATPase it is important to note that this protein
is globular and contains a series of reactive domains. These proteins contain a catalytic α-subunit
and a β-subunit which compose its molecular structure. The α-subunit is located in the
extracellular environment of the cell and the β-subunit is located in the internal environment of
the cell (Puts and Holthuis, 2009). The domains of interest within the structure are those of the
A, P, M, and N domains (Puts and Holthuis, 2009). Each region carries out a specific function,
respectively. The P domain is responsible for phosphorylation, the A domain is an activator
region, nucleotides bind at the N domain and the M domain is located structurally within the
lipid bilayer of the membrane (Puts and Holthuis, 2009). There lies an important structural
component within the M domain of this protein. A cytoplasmic loop which contains a
Corvini 2
3. Molecular Cell Biology Final Paper S.Corvini 2011
phosphorylated Asparagine residue is responsible for connecting the functional regions of the M
domain and as a result directly relate to the activity of the pump (Puts and Holthuis, 2009).
The function of the pump mechanism is rather basic in its execution. As a result of
varying levels of ions on the inside and outside of the cell warrant a need for balance to be
established. This causes for the movement of ions along an ion gradient (Smith and Crampin,
2004). As molecules of adenosine triphosphate (ATP) are hydrolyzed and used to phosphorylate
the Na+/K+-ATPase allowing for it to undergo specific conformational transitions in order to
facilitate the transport of sodium and potassium (Smith and Crampin, 2004). Occlusion of the
respective ions during conformational changes is necessary in order to prevent loss or waste of
ions during the execution of this molecular process (Apell, 1989).
After the phosphorylation of the protein there is a conformational change. Research
studies have referred to the first transformation of the molecule as the E1 conformational phase
(Apell, 1989). It is in this phase that Na+ ions become occluded within the binding sites on the
protein and are held in this position until the initiation of phase two of this molecular process
(Apell, 1989). The bind of Na+ signals the protein to return to its initial conformation, referred to
as E2 for purposes of understanding. This transition facilitates the release of Na+ ions into the
cell and allows for the occlusion of K+ ions (Apell, 1989). When the protein is again
phosphorylated and undergoes the transition back to the E1 conformation the K+ ions will be
released into the extracellular environment. In a single turn of the Na+/K+ pump there are 3 Na+
ions released for every 2 K+ ions (Apell, 1989). It is important to note that in regard to the
conformations of this protein the E1 transition prefers the binding of Na+ and ATP. As a result it
has a higher affinity for these particular ligands. The E2 transition state of the protein is more
preferential of K+ binding and possesses a higher affinity for K+ as a primary ligand.
Corvini 3
4. Molecular Cell Biology Final Paper S.Corvini 2011
The environment that integral proteins function within must also be taken into
consideration when working to understand these functional units. Lipids surround all integral
proteins within the cell membrane. Fluidity and tension of the membrane are among some of the
specific functions regulated by the lipid components of the membrane (Lee, 2004). In order to
better understand how these molecules can affect integral proteins the phosphate backbones of
the tail region can provide insight. Research done in mouse blood cells shows that two key
chemical components known as glycerophphoethanolamine (GPS) and glycerophosphoserine
(GPS) can be found (Lee, 2004). It was recorded that GPS is more reactive and contributes
positively than that of GPE. Also, the functional groups present within the head group of the
lipid structure are important to take note of because these directly interact with the functional
groups of the integral protein (Lee, 2004). This can affect the hydrophobic interactions that occur
within the inter-membrane space of the bilayer.
Polar interactions within the head region of phospholipids within the cell membrane
could affect the second structural formations within integral proteins (Lee, 2004). It is because
charged amino acids are involved in the formation the protein. As a result the head region could
cause differentiations in the internal structure by manipulating α-helix or β-sheet formation (Lee,
2004). An example of one such protein is rhodopsin which is affected by tyrosine and tryptophan
residues. As these interact with the polar head region of the lipid it is vital that the hydrophobic
interactions occur in the appropriate manner which allows for optimal functionality of the
protein. The charged nature of lipids, when interacting with charged amino acid residues that
construct the polypeptide backbone of proteins, can drastically effect the folding at the secondary
level for integral membrane proteins (Lee, 2004).
Corvini 4
5. Molecular Cell Biology Final Paper S.Corvini 2011
Symport proteins are vital to the success of the cell and to the preservation of equilibrium
on the molecular level. These integral membrane proteins regulate the transport of ions which
include Na+, K+, H+ and Ca2+ (Smith and Crampin, 2004). An area of interest regarding these
pumps involves their effect on the electronegativity of the cell membrane by affecting the cell’s
electrical potential (Johnson, 1980). The sodium potassium pump has been found to be
responsible for 5 to 40% of cell energy expenditure (O’Neil and Mikkelsen, 2004). These pumps
have been found to have different effects, both negative and positive on various cells of the body
(Johnson, 1980). The cell relies on these proteins in order to maintain functionality and structural
integrity.
Corvini 5
6. Molecular Cell Biology Final Paper S.Corvini 2011
References
E.A. Johnson, J.B. Chapman and J.M. Kootsey, Some electrophysiological consequences of
electrogenic sodium and potassium transport in cardiac muscle. J. Theor. Biol., 87 (1980),
pp. 737–756.
A.G. Lee, How lipids affect the activities of integral membrane proteins. Biochim. Biophys. Acta,
1666 (2004), pp. 62–87.
O'Neill WC and Mikkelsen RB. 1987. The role of pump number and intracellular sodium and
potassium in determining na,K pump activity in human erythrocytes. Metab Clin Exp
36(4):345-50.
Puts CF and Holthuis JCM. 2009. Mechanism and significance of P4 ATPase-catalyzed lipid
transport: Lessons from a Na+/K+-pump. Biochimica Et Biophysica Acta (BBA) -
Molecular and Cell Biology of Lipids 1791(7):603-11.
Smith NP and Crampin EJ. 2004. Development of models of active ion transport for whole-cell
modelling: Cardiac sodium–potassium pump as a case study. Prog Biophys Mol Biol 85(2-
3):387-405.
Corvini 6
