The Helen L. and Martin S. Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA.
Nature. 2012 Mar 11;483(7390):494-7. doi: 10.1038/nature10881.
The hydrosulphide ion (HS(-)) and its undissociated form, hydrogen sulphide (H(2)S), which are believed to have been critical to the origin of life on Earth, remain important in physiology and cellular signalling. As a major metabolite in anaerobic bacterial growth, hydrogen sulphide is a product of both assimilatory and dissimilatory sulphate reduction. These pathways can reduce various oxidized sulphur compounds including sulphate, sulphite and thiosulphate. The dissimilatory sulphate reduction pathway uses this molecule as the terminal electron acceptor for anaerobic respiration, in which process it produces excess amounts of H(2)S (ref. 4). The reduction of sulphite is a key intermediate step in all sulphate reduction pathways. In Clostridium and Salmonella, an inducible sulphite reductase is directly linked to the regeneration of NAD(+), which has been suggested to have a role in energy production and growth, as well as in the detoxification of sulphite. Above a certain concentration threshold, both H(2)S and HS(-) inhibit cell growth by binding the metal centres of enzymes and cytochrome oxidase, necessitating a release mechanism for the export of this toxic metabolite from the cell. Here we report the identification of a hydrosulphide ion channel in the pathogen Clostridium difficile through a combination of genetic, biochemical and functional approaches. The HS(-) channel is a member of the formate/nitrite transport family, in which about 50 hydrosulphide ion channels form a third subfamily alongside those for formate (FocA) and for nitrite (NirC). The hydrosulphide ion channel is permeable to formate and nitrite as well as to HS(-) ions. Such polyspecificity can be explained by the conserved ion selectivity filter observed in the channel's crystal structure. The channel has a low open probability and is tightly regulated, to avoid decoupling of the membrane proton gradient.
巯基离子（HS(-)）及其未离解形式硫化氢（H(2)S）被认为对地球上生命的起源至关重要，它们在生理学和细胞信号转导中仍然很重要。作为厌氧细菌生长的主要代谢物，硫化氢是同化和异化硫酸盐还原的产物。这些途径可以还原各种氧化的硫化合物，包括硫酸盐、亚硫酸盐和硫代硫酸盐。异化硫酸盐还原途径将该分子用作厌氧呼吸的末端电子受体，在此过程中会产生过量的 H(2)S（参考文献 4）。亚硫酸盐的还原是所有硫酸盐还原途径的关键中间步骤。在梭菌和沙门氏菌中，诱导型亚硫酸盐还原酶直接与 NAD(+)的再生相关联，这被认为在能量产生和生长以及亚硫酸盐的解毒中具有作用。在一定的浓度阈值以上，H(2)S 和 HS(-)通过结合酶和细胞色素氧化酶的金属中心来抑制细胞生长，这需要一种释放机制将这种有毒代谢物从细胞中排出。在这里，我们通过遗传、生化和功能方法的组合，在病原体艰难梭菌中鉴定出一种巯基离子通道。HS(-)通道是甲酸盐/亚硝酸盐转运家族的成员，其中约 50 个巯基离子通道与甲酸盐（FocA）和亚硝酸盐（NirC）通道一起形成第三个亚家族。HS(-)通道对甲酸盐和亚硝酸盐以及 HS(-)离子具有通透性。这种多特异性可以通过通道晶体结构中观察到的保守离子选择性过滤器来解释。该通道的开放概率低，受到严格调控，以避免膜质子梯度解耦。
