依賴于電壓的離子通道響應(yīng)于膜電壓的變化而打開，但發(fā)生這一過程的分子機(jī)制卻不清楚,。由MacKinnon及其同事在2003年所做的先驅(qū)性工作表明,，該過程涉及一種類脂暴露的“槳”狀結(jié)構(gòu)的運(yùn)動,，但這種運(yùn)動的性質(zhì)仍然存在爭議。在兩篇互補(bǔ)性文章的第一篇中,，Alabi等人通過證明這種“槳”狀結(jié)構(gòu)的功能在移植進(jìn)關(guān)系較遠(yuǎn)的通道中時(shí)被忠實(shí)保留下來的事實(shí),，說明了這種結(jié)構(gòu)特征的重要性。這項(xiàng)工作還強(qiáng)調(diào)了膜內(nèi)這一結(jié)構(gòu)的移動性,。Long等人描述了被由類脂排列成的一個(gè)類似于雙層的體系所包圍的一個(gè)被改變了的Kv1.2鉀通道的高分辨率結(jié)構(gòu),。“槳”狀結(jié)構(gòu)中的臨界正電荷被類脂和蛋白相互作用所穩(wěn)定，這說明了該“槳”狀結(jié)構(gòu)可能會以某種方式響應(yīng)于電壓的變化而運(yùn)動,，將該通道孔打開,。（科學(xué)網(wǎng)）
原始出處:
Nature 450, 370-375 (15 November 2007) | doi:10.1038/nature06266; Received 31 July 2007; Accepted 17 September 2007
Portability of paddle motif function and pharmacology in voltage sensors
AbdulRasheed A. Alabi1,3, Maria Isabel Bahamonde1,3, Hoi Jong Jung2, Jae Il Kim2 & Kenton J. Swartz1
Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA
Department of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, 500-712, Korea
These authors contributed equally to this work.
Correspondence to: Kenton J. Swartz1 Correspondence and requests for materials should be addressed to K.J.S. (Email: [email protected]).
Voltage-sensing domains enable membrane proteins to sense and react to changes in membrane voltage. Although identifiable S1–S4 voltage-sensing domains are found in an array of conventional ion channels and in other membrane proteins that lack pore domains, the extent to which their voltage-sensing mechanisms are conserved is unknown. Here we show that the voltage-sensor paddle, a motif composed of S3b and S4 helices, can drive channel opening with membrane depolarization when transplanted from an archaebacterial voltage-activated potassium channel (KvAP) or voltage-sensing domain proteins (Hv1 and Ci-VSP) into eukaryotic voltage-activated potassium channels. Tarantula toxins that partition into membranes can interact with these paddle motifs at the protein–lipid interface and similarly perturb voltage-sensor activation in both ion channels and proteins with a voltage-sensing domain. Our results show that paddle motifs are modular, that their functions are conserved in voltage sensors, and that they move in the relatively unconstrained environment of the lipid membrane. The widespread targeting of voltage-sensor paddles by toxins demonstrates that this modular structural motif is an important pharmacological target.
