Pedersen Bjørn P, Buch-Pedersen Morten J, Morth J Preben, Palmgren Michael G, Nissen Poul
Centre for Membrane Pumps in Cells and Disease-PUMPKIN, Danish National Research Foundation, Denmark.
Nature. 2007 Dec 13;450(7172):1111-4. doi: 10.1038/nature06417.
A prerequisite for life is the ability to maintain electrochemical imbalances across biomembranes. In all eukaryotes the plasma membrane potential and secondary transport systems are energized by the activity of P-type ATPase membrane proteins: H+-ATPase (the proton pump) in plants and fungi, and Na+,K+-ATPase (the sodium-potassium pump) in animals. The name P-type derives from the fact that these proteins exploit a phosphorylated reaction cycle intermediate of ATP hydrolysis. The plasma membrane proton pumps belong to the type III P-type ATPase subfamily, whereas Na+,K+-ATPase and Ca2+-ATPase are type II. Electron microscopy has revealed the overall shape of proton pumps, however, an atomic structure has been lacking. Here we present the first structure of a P-type proton pump determined by X-ray crystallography. Ten transmembrane helices and three cytoplasmic domains define the functional unit of ATP-coupled proton transport across the plasma membrane, and the structure is locked in a functional state not previously observed in P-type ATPases. The transmembrane domain reveals a large cavity, which is likely to be filled with water, located near the middle of the membrane plane where it is lined by conserved hydrophilic and charged residues. Proton transport against a high membrane potential is readily explained by this structural arrangement.
生命的一个先决条件是能够维持跨生物膜的电化学失衡。在所有真核生物中，质膜电位和次级转运系统由P型ATP酶膜蛋白的活性提供能量：植物和真菌中的H⁺-ATP酶（质子泵），以及动物中的Na⁺,K⁺-ATP酶（钠钾泵）。P型这个名称源于这些蛋白质利用ATP水解的磷酸化反应循环中间体这一事实。质膜质子泵属于III型P型ATP酶亚家族，而Na⁺,K⁺-ATP酶和Ca²⁺-ATP酶属于II型。电子显微镜已经揭示了质子泵的整体形状，然而，其原子结构一直缺失。在这里，我们展示了通过X射线晶体学确定的首个P型质子泵结构。十个跨膜螺旋和三个胞质结构域定义了跨质膜的ATP偶联质子转运功能单元，并且该结构锁定在P型ATP酶中以前未观察到的功能状态。跨膜结构域显示出一个大腔，它可能充满水，位于膜平面中间附近，周围排列着保守的亲水和带电荷残基。这种结构排列很容易解释质子逆高膜电位的转运。
