P-型ATP酶是對(duì)所有真核生物和很多原核生物具有根本重要性的陽離子泵。本期Nature上3篇論文介紹了關(guān)于這一超級(jí)家族關(guān)鍵成員的結(jié)構(gòu)及功能研究。本期封面所示為鈉離子和鉀離子泵的結(jié)構(gòu),，是由Morth等人在本期雜志上以3.5埃的分辨率描述的，同時(shí)還刊登了J. C. Skou關(guān)于其50年前發(fā)現(xiàn)依賴于鈉離子和鉀離子的ATP酶活性的原始筆記,。這篇論文顯示了ATP酶與鉀相結(jié)合的狀態(tài),，同時(shí)還暗示了一種依賴于電壓的調(diào)控基礎(chǔ)。這些結(jié)果部分是通過與Skou所作實(shí)驗(yàn)相似的動(dòng)能實(shí)驗(yàn)獲得的,。Olesen等人介紹了肌質(zhì)網(wǎng)Ca2+-ATP酶(鈣泵)的新的晶體結(jié)構(gòu),，同時(shí)還有關(guān)于功能的研究工作，并且最終呈現(xiàn)了關(guān)于鈣運(yùn)輸?shù)囊粋€(gè)完整機(jī)制,。在植物和真菌中,，細(xì)胞離子平衡狀態(tài)和膜勢(shì)是由胞質(zhì)膜H+-ATP酶(另一種P-型ATP酶)提供動(dòng)力的。Pedersen等人介紹了它的X-射線結(jié)構(gòu),，提供了關(guān)于它是如何沿一個(gè)陡峭的電化學(xué)梯度來泵輸質(zhì)子的有關(guān)線索,。
原始出處:
Nature 450, 1036-1042 (13 December 2007) | doi:10.1038/nature06418; Received 13 August 2007; Accepted 26 October 2007
The structural basis of calcium transport by the calcium pump
Claus Olesen1,2, Martin Picard3,4, Anne-Marie Lund Winther1,3, Claus Gyrup3, J. Preben Morth1,3, Claus Oxvig3, Jesper Vuust Møller1,2 & Poul Nissen1,3
Centre for Membrane Pumps in Cells and Disease—PUMPKIN, Danish National Research Foundation, and,
Institute of Physiology and Biophysics, University of Aarhus, Ole Worms Alle, blg. 1185, DK - 8000 Aarhus C, Denmark
Department of Molecular Biology, University of Aarhus, Gustav Wieds Vej 10C, DK - 8000 Aarhus C, Denmark
Present address: Laboratoire de Cristallographie et RMN biologiques, UMR 8015 CNRS, Faculté de Pharmacie. Université Paris Descartes, 4 avenue de l'Observatoire, 75270 Paris Cedex 06, France.
Correspondence to: Jesper Vuust Møller1,2Poul Nissen1,3 Correspondence and requests for materials should be addressed to P.N. (Email: [email protected]) and J.V.M. (Email: [email protected]).
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Abstract
The sarcoplasmic reticulum Ca2+-ATPase, a P-type ATPase, has a critical role in muscle function and metabolism. Here we present functional studies and three new crystal structures of the rabbit skeletal muscle Ca2+-ATPase, representing the phosphoenzyme intermediates associated with Ca2+ binding, Ca2+ translocation and dephosphorylation, that are based on complexes with a functional ATP analogue, beryllium fluoride and aluminium fluoride, respectively. The structures complete the cycle of nucleotide binding and cation transport of Ca2+-ATPase. Phosphorylation of the enzyme triggers the onset of a conformational change that leads to the opening of a luminal exit pathway defined by the transmembrane segments M1 through M6, which represent the canonical membrane domain of P-type pumps. Ca2+ release is promoted by translocation of the M4 helix, exposing Glu 309, Glu 771 and Asn 796 to the lumen. The mechanism explains how P-type ATPases are able to form the steep electrochemical gradients required for key functions in eukaryotic cells.
