波城新语 - 笑人也笑己，笑笑无坏意， 读读就算了，千万别生气！
冬雪倘雅淡，不走也不嫌，春風若溫暖，遲到也喜歡。
小颜为何引他的
最近对小颜发现葡萄糖转运体晶体结构的争吵，仍处在僵持状态。在多次转移焦点后，最近的焦点是所谓的机理，按照控方的逻辑，小Yan提出的模型或机理和大Yan的一样，但是却在文中刻意没有提到大Yan的模型，所以是科学不轨的行为。
更有人说不信小Yan当时没有读大Yan的文章，并说如果她再不承认就派人去她在京的科研组去查《细胞》杂志，如果看见大Yan的那篇文章被弄得皱巴巴的，就是物证或者是smoking gun，似乎这样就能让那小妖精必死无疑。哈哈，就像是读哈尔姆斯一样，乖乖，又让我想写一篇微小说了, 题目叫：教授进京捉小妖。
可是，真正好的侦探不是只叫不查的，好的侦探，即使像我这样业余的，也会静下心了，请华为和小哥一起帮忙，在两人还没有完全翻脸之前，弄清事情真相，还被冤枉的人一个清白。
那各位看官看到这里说你这个人不仅又黄又专，还又啰嗦。是的，这个案子一日不定案，我就罗嗦一天，直到烦死城里的大Yan粉和小Yan黑。今天给大家谈谈小颜为什么不引用大Yan的文章，却偏偏去引用一个叫姐夫－阿布染木森（Jeff Abramson）的无名小辈的文。
原来这个人比大Yan还厉害，他就是第一个弄清细菌上糖转移体结构和机理的第一人，但他不是葡萄糖的，所以只要小Yan不说她是搞清单糖，而是说单糖之一的葡萄糖转移体结构和机理的第一人就没有问题。
那你可能要说，你这个黄阿哥，别给我们兜圈子了，快把干货拿出来。好的，上干货（英文怎么说: above dry goods？），原来这个人在美国的《科学》杂志上发表了大肠杆菌的乳糖转运体(又称乳糖通透酶）的晶体结构。一起看看他们那文的摘要：
Structure and Mechanism of the Lactose Permease of Escherichia coli
Jeff Abramson,1 Irina Smirnova,3 Vladimir Kasho,3 Gillian Verner,3 H. Ronald Kaback,3* So Iwata1,2* Science. 2003 Aug 1;301(5633):610-5.
Membrane transport proteins that transduce free energy stored in electrochemical ion gradients into a concentration gradient are a major class of membrane proteins. We report the crystal structure at 3.5 angstroms of the Escherichia coli lactose permease, an intensively studied member of the major facilitator superfamily of transporters. The molecule is composed of N- and C-terminal domains, each with six transmembrane helices, symmetrically positioned within the permease. A large internal hydrophilic cavity open to the cytoplasmic side represents the inward-facing conformation of the transporter. The structure with a bound lactose homolog, -D-galactopyranosyl-1-thio--D-galactopyranoside, reveals the sugar-binding site in the cavity, and residues that play major roles in substrate recognition and proton translocation are identified. We propose a possible mechanism for lactose/proton symport (cotransport) consistent with both the structure and a large body of experimental data.
将存储在电化学离子梯度中的自由能转换成浓度梯度的膜转运蛋白是一类主要的膜蛋白。我们在这报告大肠杆菌乳糖通透酶3.5埃的晶体结构，这是一个被广泛研究的转运蛋白主要促进子超家族成员。该分子由N和N组成C末端结构域，每个具有六个跨膜螺旋，对称地定位在通透酶内。通向细胞质侧的大的内部亲水腔表示转运蛋白的向内构象。与结合的乳糖同源，-D吡喃半乳糖基-1-硫代 - D-吡喃半乳糖苷揭示了腔中的糖结合位点，并且鉴定了在底物识别和质子易位中起主要作用的残基。我们提出了乳糖/质子同向（共转运）的可能机理，与结构和大量实验数据一致。
说到这里，你可能说黄阿哥在胡说什么呢？连小喇叭都没有，我们大Yan的机理是小喇叭，难道你没有看到他用双手比划那小喇叭时那激动的的样子吗？没有，我只看到不少大妈和暖男跳小苹果。
好了，小喇叭就小喇叭吧：
这个像不像小喇叭？
Science. 2003 Aug 1;301(5633):610-5.
如果不像，这个呢？
Science. 2003 Aug 1;301(5633):610-5.
在这个图里，小阿很清楚地提出了单糖转运体的晶体结构，转运的模型和小喇叭机理（小哥翻译成机制，被我教训了一顿，说你不知道大Yan说的是机理吗？）。
有人说你这个黄阿哥不是一直都在说相关性吗? 难道这个基因比大Yan那个基因更有相关性？答案是，是的。虽然从基因的角度讲也是另外一个基因，但是人家这个也是一个大家庭的，而且他的结构和机理都比较完整，不仅完整而且还更新。在这种情况下，如果是你你会选用谁的引用呢？小Yan毫不犹豫地决定选用小阿的。在黄阿哥看来是绝对合情合理，没有一点避重就轻的嫌疑。
还有一点黄阿哥要想大家汇报，那就是小阿也同样没有引用大Yan的结果。这这这，这不是合伙来欺负我们的文城一博大Yan吗？这是什么世道呀！
我去哈哈了几声，说“人外有人 天外有天”。他恼了…：）
其实每个人的知识都是有局限性的，尊重他人，尊重事实，“真正的尊重科学真理”，很重要，这才是一个科学家的精神。
生物学发展很快，我们有幸看到Car T ，PD-1等用于肿瘤治疗，和基因治疗药物的时代到来，并且仍然努力做事。
无论成败，都是英雄，所以我引用“老人与海”的故事。
他93年做的工作采用的分子生化技术怎么会是研究“活蛋白”？
我这个技校毕业的更要humble 了, 看来得请’教授’来帮助涨知识了.
Model of the mechanism of uniport transport by GLUT1, which is believed to shuttle between two conformational states
In one conformation (?1?, ?2?, and ?5?), the glucose-binding site faces outward; in the other (?3?, ?4?), the binding site faces inward. Binding of glucose to the outward-facing binding site (?1? →? 2?) triggers a conformational change in the transporter (?2? →? 3?), moving the bound glucose through the protein such that it is now bound to the inward-facing binding site. Glucose can then be released to the inside of the cell (?3? → ?4?). Finally, the transporter undergoes the reverse conformational change (?4? →? 5?), inactivating the inward-facing glucose binding site and regenerating the outward-facing one. If the concentration of glucose is higher inside the cell than outside, the cycle will work in reverse (?4? →??1?), catalyzing net movement of glucose from inside to out.
From: Section 15.3, Uniporter-Catalyzed Transport
Cover of Molecular Cell Biology
Molecular Cell Biology. 4th edition.
Lodish H, Berk A, Zipursky SL, et al.
有什么大不了的? 幽默一把.
幽默感去哪了?
Research Interests:
Membrane transport proteins are responsible for many critical biological functions including governing energy transduction, modifying ion concentrations, and actively importing metabolites into the cell. Membrane proteins represent 20-30% of all proteins in each of the sequenced genomes. In addition, they are targets for 50% of all marketed drugs. Considering their biological and pharmacological relevance and their vast numbers throughout genomes, there is an enormous demand for structural information. However, membrane proteins represent only about ~0.7% of the protein structures in the Protein data bank. The reason for this discrepancy stems from the hydrophobic nature of membrane proteins, which reside in a phospholipid bilayer, making them difficult to express, purify, and crystallize.
Our lab is trying to overcome these barriers and resolve the structures of several channels and transporters. This is an ideal format for students to interact with other groups and learn numerous techniques through interdepartmental collaborations.
Representative Publications:
Ujwal R, Cascio D, Colletier JP, Faham S, Zhang J, Toro L, Ping P, Abramson J (2008). The crystal structure of mouse VDAC1 at 2.3 A resolution reveals mechanistic insights into metabolite gating. Proc Natl Acad Sci U S A. Nov 18;105(46):17742-7.
Faham S, Watanabe A, Besserer GM, Cascio D, Specht A, Hirayama BA, Wright EM, Abramson J (2008). The crystal structure of a sodium galactose transporter reveals mechanistic insights into Na+/sugar symport. Science. Aug 8;321(5890):810-4.
Abramson J, Smirnova I, Kasho V, Verner G, Kaback HR, Iwata S. (2003). Structure and mechanism of the lactose permease of Escherichia coli. Science. 301(5633):610-5.