The energy conversion in active transport of ions

Abstract

Since their discovery in the middle of the last century (1), with the subsequent Nobel prize to Skou in 1997, the family of biological ion pumps (2⇓–4) has posed a challenge to the scientific community at large. The pumps utilize the Gibbs energy of hydrolysis of adenosine triphosphate (ATP) to move ions uphill across a membrane. How do they function? A much-studied case is Ca-ATPase (adenosine triphosphatase), which acts to control the level of the Ca<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:msup><mml:mrow></mml:mrow><mml:mrow><mml:mn>2</mml:mn><mml:mo>+</mml:mo></mml:mrow></mml:msup></mml:mrow></mml:math> content in muscle (Fig. 1 has a schematic representation). When inactive, the pump forms a closed gate in the lipid membrane. The gate opens to the internal side when ATP is supplied to the external side of the membrane. The computational results of Kobayashi et al. (5) in PNAS provide support for several critical events. First is the release of calcium ions during opening, following right after a structural change in Ca-ATPase. Next is the rapid protonation of side chains that prevents rebinding of Ca<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:msup><mml:mrow></mml:mrow><mml:mrow><mml:mn>2</mml:mn><mml:mo>+</mml:mo></mml:mrow></mml:msup></mml:mrow></mml:math>, combined with interactions between lipid molecules and transmembrane helices that help stabilize the structure. Using rare event molecular dynamics simulations, Kobayashi et al. (5) captured the structural changes in great detail and obtained Gibbs energy profiles that demonstrate the importance of a rapid exchange between Ca<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:msup><mml:mrow></mml:mrow><mml:mrow><mml:mn>2</mml:mn><mml:mo>+</mml:mo></mml:mrow></mml:msup></mml:mrow></mml:math> ions and protons upon the release of Ca<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:msup><mml:mrow></mml:mrow><mml:mrow><mml:mn>2</mml:mn><mml:mo>+</mml:mo></mml:mrow></mml:msup></mml:mrow></mml:math>. Fig. 1 Schematic representation of two of the enzyme states studied by Kobayashi et al. (5): the adenosine diphosphate (ADP)–sensitive phosphoenzyme state, “E1P,” and the low-energy phosphoenzyme state, ”E2p_dp.” The structures were obtained from the supporting information in ref. 5. Here, E1P denotes the state of the enzyme where ADP and Ca<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:msup><mml:mrow></mml:mrow><mml:mrow><mml:mn>2</mml:mn><mml:mo>+</mml:mo></mml:mrow></mml:msup></mml:mrow></mml:math> ions (both shown in orange) are bound to it. The ions are bound deeper within the transmembrane helices but are here … [↵][1]2To whom correspondence may be addressed. Email: anders.lervik{at}ntnu.no. [1]: #xref-corresp-1-1

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