Crystal structure of a membrane-embedded H+-translocating pyrophosphatase

Shih Ming Lin, Jia Yin Tsai, Chwan Deng Hsiao, Yun Tzu Huang, Chen Liang Chiu, Mu Hsuan Liu, Jung Yu Tung, Tseng Huang Liu, Rong Long Pan, Yuh Ju Sun

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Abstract

H+-translocating pyrophosphatases (H+-PPases) are active proton transporters that establish a proton gradient across the endomembrane by means of pyrophosphate (PP i) hydrolysis. H+-PPases are found primarily as homodimers in the vacuolar membrane of plants and the plasma membrane of several protozoa and prokaryotes. The three-dimensional structure and detailed mechanisms underlying the enzymatic and proton translocation reactions of H+-PPases are unclear. Here we report the crystal structure of a Vigna radiata H+-PPase (VrH+-PPase) in complex with a non-hydrolysable substrate analogue, imidodiphosphate (IDP), at 2.35 Å resolution. Each VrH+-PPase subunit consists of an integral membrane domain formed by 16 transmembrane helices. IDP is bound in the cytosolic region of each subunit and trapped by numerous charged residues and five Mg2+ ions. A previously undescribed proton translocation pathway is formed by six core transmembrane helices. Proton pumping can be initialized by PP i hydrolysis, and H+ is then transported into the vacuolar lumen through a pathway consisting of Arg 242, Asp 294, Lys 742 and Glu 301. We propose a working model of the mechanism for the coupling between proton pumping and PP i hydrolysis by H+-PPases.

Original languageEnglish
Pages (from-to)399-403
Number of pages5
JournalNature
Volume484
Issue number7394
DOIs
Publication statusPublished - 2012 Apr 19

All Science Journal Classification (ASJC) codes

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    Lin, S. M., Tsai, J. Y., Hsiao, C. D., Huang, Y. T., Chiu, C. L., Liu, M. H., Tung, J. Y., Liu, T. H., Pan, R. L., & Sun, Y. J. (2012). Crystal structure of a membrane-embedded H+-translocating pyrophosphatase. Nature, 484(7394), 399-403. https://doi.org/10.1038/nature10963