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It is thanks to proteins in the nose called odour receptors that we find the smell of roses pleasant and that of rotting food foul. But little is known about how these receptors detect molecules and translate them into scents.正是由于鼻子中被称为气味受体的蛋白质，我们才发现玫瑰的气味令人愉快，而腐烂食物的气味令人讨厌。但人们对这些受体如何检测分子并将其转化为气味知之甚少。Now, for the first time, researchers have mapped the precise 3D structure of a human odour receptor, taking a step forwards in understanding the most enigmatic of our senses.现在，研究人员首次绘制了人类气味受体的精确3D结构图，在理解我们最神秘的感官方面迈出了一步。The study, published in Nature on 15 March1, describes an olfactory receptor called OR51E2 and shows how it ‘recognizes’ the smell of cheese through specific molecular interactions that switch the receptor on.这项研究于3月15日发表在《自然》杂志上，描述了一种名为OR51E2的嗅觉受体，并展示了它如何通过特定的分子相互作用来“识别”奶酪的气味，从而打开受体。“It’s basically our first picture of any odour molecule interacting with one of our odour receptors,” says study co-author Aashish Manglik, a pharmaceutical chemist at the University of California, San Francisco.“这基本上是我们第一次看到任何气味分子与我们的气味受体相互作用的图片，”研究合著者、旧金山加州大学药物化学家Aashish Manglik说。The human genome contains genes encoding 400 olfactory receptors — first discovered by Richard Axel and Lina Buck in 19912 — that detect many odours. Researchers in the 1920s estimated that the human nose could discern around 10,000 smells3, but a 2014 study suggests that we can distinguish more than one trillion scents4.人类基因组包含编码400个嗅觉受体的基因，这些嗅觉受体于19912年由Richard Axel和Lina Buck首次发现，可以检测许多气味。20世纪20年代的研究人员估计，人类的鼻子可以分辨出大约10000种气味3，但2014年的一项研究表明，我们可以分辨出超过一万亿种气味4。Each olfactory receptor can interact with only a subset of smelly molecules called odorants — and a single odorant can activate multiple receptors. It is “like hitting a chord on a piano”, says Manglik. “Instead of hitting a single note, it's a combination of keys that are hit that gives rise to the perception of a distinct odour.”每个嗅觉受体只能与一种称为气味分子的气味分子子集相互作用，而一种气味分子可以激活多个受体。曼格里克说，这“就像在钢琴上弹奏和弦”。“它不是敲击一个音符，而是敲击多个键的组合，产生一种独特的气味。”Beyond this, little is known about exactly how olfactory receptors recognize specific odorants and encode different smells in the brain.除此之外，人们对嗅觉受体如何识别特定的气味并在大脑中编码不同的气味知之甚少。Technical challenges in producing mammalian olfactory-receptor proteins using standard laboratory methods have made it difficult to study how these receptors bind to odorants.使用标准实验室方法生产哺乳动物嗅觉受体蛋白的技术挑战使得研究这些受体如何与气味物质结合变得困难。“Almost all of them really don't like being in any other kind of cell other than an olfactory sensory neuron,” says Matthew Grubb, a neuroscientist at King’s College London. This means that they cannot be grown or stabilized in commonly used cell lines. “You would have to dissect probably thousands of mice noses” to replicate samples, says Grubb. “It’s just not feasible.”伦敦国王学院的神经科学家Matthew Grubb说：“几乎所有人都不喜欢呆在嗅觉感觉神经元之外的任何其他类型的细胞里。”。这意味着它们不能在常用的细胞系中生长或稳定。Grubb说，“你可能需要解剖数千只老鼠的鼻子”才能复制样本。“这是不可行的。”To overcome this, Manglik and his colleagues focused on the OR51E2 receptor, which has functions beyond odorant recognition and is found in gut, kidney and prostate tissues, as well as olfactory neurons.为了克服这一点，Manglik和他的同事专注于OR51E2受体，该受体的功能超出了气味识别，存在于肠道、肾脏和前列腺组织以及嗅觉神经元中。OR51E2 interacts with two odorant molecules: acetate, which smells like vinegar, and propionate, which has a cheesy odour.OR51E2与两种气味分子相互作用：乙酸盐，闻起来像醋，丙酸盐，有奶酪味。The authors purified OR51E2 and analysed its structure with and without propionate using cryo-electron microscopy, an atomic-resolution imaging technique. They also used computer-aided simulations to model how the protein interacts with the odorant at an atomic scale.作者纯化了OR51E2，并使用冷冻电子显微镜（一种原子分辨率成像技术）分析了含有和不含有丙酸盐的OR51E2的结构。他们还使用计算机辅助模拟来模拟蛋白质如何在原子尺度上与气味物质相互作用。They found that propionate binds OR51E2 through specific ionic and hydrogen bonds that anchor the propionate’s carboxylic acid to an amino acid, arginine, in a region of the receptor called the binding pocket. Binding to propionate alters the shape of OR51E2, which is what turns the receptor on.他们发现丙酸盐通过特定的离子和氢键与OR51E2结合，这些离子和氢键将丙酸盐的羧酸锚定在受体的一个称为结合袋的区域中的氨基酸精氨酸上。与丙酸盐的结合改变了OR51E2的形状，这就是开启受体的原因。These molecular interactions are crucial: the researchers showed that mutations affecting arginine prevented OR51E2 from being activated by propionate.这些分子相互作用至关重要：研究人员表明，影响精氨酸的突变阻止了OR51E2被丙酸盐激活。“This is our way of kind of lining up the dominoes to understand how pushing on one side of the receptor turns the other side on,” says Manglik.Manglik说：“这是我们排列多米诺骨牌的方式，以了解推动受体的一侧是如何打开另一侧的。”。It has been a long-term dream for scientists to build a molecular atlas of olfactory receptors that maps their chemical structures and which combinations of receptors correspond to particular odours. But “that’s been very much out of reach for the field”, says Manglik.建立嗅觉受体的分子图谱，绘制它们的化学结构，以及受体的哪些组合对应于特定的气味，这是科学家们的长期梦想。但曼格里克表示，“这对该领域来说是遥不可及的”。The OR51E2 receptor is specific to propionate and acetate. But “it's not all about single odorant binding to single receptor molecules”, says Grubb. OR51E2 is a class I olfactory receptor; only around 10% of human olfactory receptor genes encode this type. The rest code for class II receptors, which typically recognize a broader range of odours. “They may have very different mechanisms,” says Vanessa Ruta, a neuroscientist at the Rockefeller University in New York City.OR51E2受体对丙酸盐和乙酸盐具有特异性。但Grubb说，“这并不全是单个气味剂与单个受体分子的结合”。OR51E2是一种I类嗅觉受体；只有大约10%的人类嗅觉受体基因编码这种类型。其余的是II类受体的编码，它们通常能识别更广泛的气味。“它们可能有非常不同的机制，”纽约市洛克菲勒大学的神经科学家Vanessa Ruta说。Studying other examples of human odour receptors and elucidating their structures is crucial, she adds. “It will allow for a broader understanding of the different ways that odorants are recognized.”她补充道，研究人类气味受体的其他例子并阐明它们的结构至关重要。“这将有助于更广泛地了解气味识别的不同方式。”高级词汇：1. odour receptors - 气味受体
2. molecules - 分子
3. enigmatic - 神秘的
4. mapped - 绘制
5. olfactory receptor - 嗅觉受体
6. molecular interactions - 分子间相互作用
7. activate - 激活
8. genome - 基因组
9. odorants - 气味物质
10. distinguish - 区分
11. chord - 和弦
12. encoding - 编码
13. technical challenges - 技术挑战
14. stabilized - 稳定
15. atomic-resolution imaging - 原子分辨率成像
16. interactions - 相互作用
17. mutations - 突变
18. atlas - 地图
19. elucidating - 阐明
主旨大意：该研究通过绘制人类气味受体的精确三维结构，揭示了人类嗅觉感知机制的一部分，但仍不完整。此外，研究人员面临着技术上的挑战，因为嗅觉受体蛋白在除嗅觉感受神经元之外的任何其他细胞或细胞系中生长或稳定都比较困难。
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