AN INTEGRATED, ANIMATED MODEL OF THE (NA, K)-ATPase HYDROLYTIC CYCLE

• Autor(a) principal: Leone, F.A.
• Data de Publicação: 2006
• Outros Autores: Furriel, R.P.M., McNamara, J.C, Borin, I.A., Horisberger, J.D
• Tipo de documento: Artigo
• Idioma: por
• Título da fonte: Revista de Ensino de Bioquímica
• Texto Completo: http://bioquimica.org.br/revista/ojs/index.php/REB/article/view/54
• topic: HYDROLYTIC CYCLE, (NA, K)-ATPase

The  (Na,  K)-ATPase,  or  sodium  pump,  is  the  principal,  active  transport  system  that  establishes  sodium  and potassium  gradients  across  the  plasma  membranes  of  all  animal  cells.  Such  gradients  are  critical  to  sustaining important cellular functions like osmotic equilibrium, cell volume and pH homeostasis, among many others (Ann Rev Physiol 65: 817, 2003; Physiol 19: 377, 2004). This transport protein is a heterodimer that consists of a 110-kDa  -subunit  and  a  55-kDa,  glycosylated  -subunit.  A  group  of  seven  small  proteins,  known  as  FXYD  proteins  from  the sequence  of  a  conserved  motif  has  been  identified  recently,  and  one  of  these,  FXYD2,  constitutes  the  (Na,  K)-ATPase  -subunit.  Our  model  is  based  on  conformational  changes  occurring  between  the  E1  and  E2  forms  of  the enzyme, which initiates its hydrolytic cycle at a high ATP/ADP ratio. While all steps are reversible, the model does not include  the reverse  reactions that can  take  place under appropriate conditions. The  E1 state  corresponds to that of the SERCA, recently crystallized (Science 304; 1672, 2004; Nature 430: 529, 2004). The animation was developed in Macromedia  Flash  8.0® and  illustrates  the  principle  of  an  alternating-access  model  of  an  ion  pump.  The  protein  is embedded  in  the  membrane  with  the  extracellular  face  uppermost  and  the  cytoplasmic  face  at  the  bottom.  Access from  the  cytoplasmic  or  extracellular  faces  to  the  cation-binding  sites,  located  in  the  transmembrane  moiety,  are controlled  by  two  gates  (moving  horizontal  bars),  and  conformations  showing  the  two  gates  closed  correspond  to states with occluded Na+ and K+ sites. Changes in cation-binding site structure entail selective modifications of cation affinity. As the animation proceeds, the mechanism revealing the different steps of enzyme activity can be accessed through a pop-up window. A key explaining the different animation elements is also provided