Molecular cell final paper

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Final paper on sodium/potassium pump.

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Molecular cell final paper

  1. 1. MANHATTANVILLE COLLEGE The Na+/K+ PumpA Discussion of structural and functional importance in the cell membrane Stephen Corvini 11/30/2011 Dr. Bettica Molecular Cell Biology
  2. 2. Molecular Cell Biology Final Paper S.Corvini 2011Stephen CorviniMolecular Cell BiologyFinal PaperDr. BetticaNovember 30, 2011 The sodium potassium pump resides as a core example of an ATP driven symportchannel protein that exists within the cell membrane. It is a primary transport sarcolemmaltransport protein that works to maintain the ion gradient between sodium and potassium ionswithin the external and internal cellular environment (Smith and Crampin, 2004). As a memberof the integrin protein family this structure is rooted within the lipid bilayer and possesses amultiple 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. Throughthe addition and subtraction of phosphates from the protein conformational changes occur whichallow 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 proteinis globular and contains a series of reactive domains. These proteins contain a catalytic α-subunitand a β-subunit which compose its molecular structure. The α-subunit is located in theextracellular environment of the cell and the β-subunit is located in the internal environment ofthe cell (Puts and Holthuis, 2009). The domains of interest within the structure are those of theA, 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 activatorregion, nucleotides bind at the N domain and the M domain is located structurally within thelipid bilayer of the membrane (Puts and Holthuis, 2009). There lies an important structuralcomponent within the M domain of this protein. A cytoplasmic loop which contains a Corvini 2
  3. 3. Molecular Cell Biology Final Paper S.Corvini 2011phosphorylated Asparagine residue is responsible for connecting the functional regions of the Mdomain 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 ofvarying levels of ions on the inside and outside of the cell warrant a need for balance to beestablished. 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 phosphorylatethe Na+/K+-ATPase allowing for it to undergo specific conformational transitions in order tofacilitate the transport of sodium and potassium (Smith and Crampin, 2004). Occlusion of therespective ions during conformational changes is necessary in order to prevent loss or waste ofions during the execution of this molecular process (Apell, 1989). After the phosphorylation of the protein there is a conformational change. Researchstudies 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 theprotein 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 toas E2 for purposes of understanding. This transition facilitates the release of Na+ ions into thecell and allows for the occlusion of K+ ions (Apell, 1989). When the protein is againphosphorylated and undergoes the transition back to the E1 conformation the K+ ions will bereleased 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 theconformations of this protein the E1 transition prefers the binding of Na+ and ATP. As a result ithas a higher affinity for these particular ligands. The E2 transition state of the protein is morepreferential of K+ binding and possesses a higher affinity for K+ as a primary ligand. Corvini 3
  4. 4. Molecular Cell Biology Final Paper S.Corvini 2011 The environment that integral proteins function within must also be taken intoconsideration when working to understand these functional units. Lipids surround all integralproteins within the cell membrane. Fluidity and tension of the membrane are among some of thespecific functions regulated by the lipid components of the membrane (Lee, 2004). In order tobetter understand how these molecules can affect integral proteins the phosphate backbones ofthe tail region can provide insight. Research done in mouse blood cells shows that two keychemical components known as glycerophphoethanolamine (GPS) and glycerophosphoserine(GPS) can be found (Lee, 2004). It was recorded that GPS is more reactive and contributespositively than that of GPE. Also, the functional groups present within the head group of thelipid structure are important to take note of because these directly interact with the functionalgroups of the integral protein (Lee, 2004). This can affect the hydrophobic interactions that occurwithin the inter-membrane space of the bilayer. Polar interactions within the head region of phospholipids within the cell membranecould affect the second structural formations within integral proteins (Lee, 2004). It is becausecharged amino acids are involved in the formation the protein. As a result the head region couldcause 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 tryptophanresidues. As these interact with the polar head region of the lipid it is vital that the hydrophobicinteractions occur in the appropriate manner which allows for optimal functionality of theprotein. The charged nature of lipids, when interacting with charged amino acid residues thatconstruct the polypeptide backbone of proteins, can drastically effect the folding at the secondarylevel for integral membrane proteins (Lee, 2004). Corvini 4
  5. 5. Molecular Cell Biology Final Paper S.Corvini 2011 Symport proteins are vital to the success of the cell and to the preservation of equilibriumon the molecular level. These integral membrane proteins regulate the transport of ions whichinclude Na+, K+, H+ and Ca2+ (Smith and Crampin, 2004). An area of interest regarding thesepumps involves their effect on the electronegativity of the cell membrane by affecting the cell’selectrical potential (Johnson, 1980). The sodium potassium pump has been found to beresponsible for 5 to 40% of cell energy expenditure (O’Neil and Mikkelsen, 2004). These pumpshave 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 structuralintegrity. Corvini 5
  6. 6. Molecular Cell Biology Final Paper S.Corvini 2011 ReferencesE.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.ONeill 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

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