Håkansson K O, Jorgensen P L
Biomembrane Center, August Krogh Institute, University of Copenhagen, Denmark.
Ann N Y Acad Sci. 2003 Apr;986:163-7. doi: 10.1111/j.1749-6632.2003.tb07155.x.
Identification of the third Na(+) binding site would be crucial in interpretation of the electrophysiological behavior of Na,K-ATPase. To address this question a three-dimensional homology model of Na,K-ATPase was built from the known crystallographic structure of Ca-ATPase (1EUL). Phe760, which is conserved in virtually all Ca-ATPases, is replaced by Ser768 in Na,K-ATPase, resulting in a small cavity between M4, M5, and M6. A partially hydrated Na(+) ion can be bound at this third site on the cytoplasmic side of cation binding sites 1 and 2. This leads to the proposal that the conductance of the "third Na(+)" ion across approximately 70% of the membrane dielectric may be achieved by adding up the passage of one Na(+) ion from the described cytoplasmic cavity to cation site 1 and the further conductance of the previously bound Na(+) ion from cation site 1 to the extracellular phase. This relay mechanism may therefore be compatible with the electrogenic profile of Na(+) translocation.
确定第三个钠离子结合位点对于解释钠钾ATP酶的电生理行为至关重要。为了解决这个问题，我们根据已知的钙ATP酶晶体结构（1EUL）构建了钠钾ATP酶的三维同源模型。在几乎所有钙ATP酶中都保守的苯丙氨酸760在钠钾ATP酶中被丝氨酸768取代，导致在M4、M5和M6之间形成一个小腔。一个部分水合的钠离子可以结合在阳离子结合位点1和2细胞质侧的这个第三个位点上。这就提出了一个观点，即“第三个钠离子”穿过大约70%膜电介质的传导可能是通过将一个钠离子从所述细胞质腔传递到阳离子位点1以及先前结合在阳离子位点1的钠离子进一步传导到细胞外相来实现的。因此，这种中继机制可能与钠离子转运的生电特性相兼容。
