台大中研院攜手 解七穿膜蛋白質秘密 2015-12-17 16:38 中央社 台北17日電 七穿膜蛋白質存在地球30億年，許多藥物研發都和它相關，台大和中研院合作，解開台灣第一個七穿膜的蛋白質結構，將有助於提升其產生能量的潛能。台大生化科技系副教授楊(啟)伸的「結構與感光生物實驗室」和中研院副院長王惠鈞實驗室合作，由團隊成員台大博士傅煦媛、中研院博士許敏峰歷經多年研究，終於解出台灣第一個七穿膜的蛋白質結構，研究成果也刊登在國際期刊上。研究團隊表示，七穿膜蛋白質是大自然原生設計，用來將光能轉成生物能的巧妙裝置，目前廣泛存在一些喜歡極端環境菌類中，如台灣南部的鹽田中的嗜鹽古生菌，但七穿膜蛋白質很難大量取得，研究團隊歷經多年研究終於有成果。在研究過程中，團隊發現有個獨特的蛋白質穩定性強，在別的同類蛋白質不能產生能量的環境下，還能繼續產能，根據其結構發現此蛋白質有個特別設計的「蓋子」，能區隔蛋白質內部和外在環境，也讓科學界為此類蛋白質分出一個新群組。研究團隊表示，七穿膜蛋白質可能已在地球存在30億年，人類的視覺、聽覺、嗅覺、腦神經、許多荷爾蒙作用，都由這類七穿膜蛋白質負責，目前市面上藥物，有一半以上都和其相關，這次解出七穿膜蛋白質結構，將可使其產生能量的潛能提高約2至10倍，可說是近40年來的重大進展。
Structural and Functional Studies of a Newly Grouped Haloquadratum walsbyi Bacteriorhodopsin Reveal the Acid-resistant Light-driven Proton Pumping Activity Retinal bound light-driven proton pumps are widespread in eukaryotic and prokaryotic organisms. Among these pumps, bacteriorhodopsin (BR) proteins cooperate with ATP synthase to convert captured solar energy into a biologically consumable form, ATP. In an acidic environment or when pumped-out protons accumulate in the extracellular region, the maximum absorbance of BR proteins shifts markedly to the longer wavelengths. These conditions effect the light-driven proton pumping functional exertion as well. In this study, wild-type crystal structure of a BR with optical stability under wide pH range from a square halophilic archaeon, Haloquadratum walsbyi (HwBR), was solved in two crystal forms. One crystal form, refined to 1.85 Å resolution, contains a trimer in the asymmetric unit, while another contains an antiparallel dimer was refined at 2.58 Å. HwBR could not be classified into any existing subgroup of archaeal BR proteins based on the protein sequence phylogenetic tree, and it showed unique absorption spectral stability when exposed to low pH values. All structures showed a unique hydrogen-bonding network between R82 and T201, linking the BC and FG loops to shield the retinal-binding pocket in the interior from the extracellular environment. This result was supported by R82E mutation that attenuated the optical stability. The negatively charged cytoplasmic side and the R82-T201 hydrogen bond may play an important role of the proton translocation trend in HwBR under acidic condition. Our findings have unveiled a strategy adopted by BR proteins to solidify their defenses against unfavorable environments and maintain their optical properties associated with proton pumping.
Source: http://www.jbc.org/content/early/2015/10/19/jbc.M115.685065.long
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