报告题目：Structural Investigations of the Voltage-gated Sodium Channel
报告人： 颜宁 博士
清华大学医学院教授
HHMI青年科学家
主持人： 冯新华 教授
时 间： 2012年10月19日（星期五）下午4：00
地 点： 医学院综合楼307室
报告人简介：
颜宁，清华大学医学院教授。2000年获清华大学生物科学与技术系学士，2004年获美国普林斯顿大学分子生物学系博士学位。2005年至2007年在普林斯顿大学进行博士后研究。2007年回到清华大学任研究员，组建自己的实验室。2011年当选“中国科学年度人物”之年度新闻人物。2012入选“霍华德—休斯医学研究所（HHMI）首届国际青年科学家奖”。在Nature，Science，Cell等国际主流杂志发表过数十篇学术研究论文，目前还是Cell Reports, Journal of Biological Chemistry的Editorial Board。
研究兴趣：
主要集中在次级主动运输蛋白（secondary active transporters）的工作机理上。交替通路模型（alternating-access model）被用来解释转运蛋白的工作机理，在这个模型中，转运蛋白至少采取两种构象来进行底物的装载及卸载：一种向膜外开放，一种向膜内开放。有许多结构和生物物理学证据支持这个模型。但是，仍有两个最有趣的基本问题没有解决。第一,主动运输的能量偶联机制是什么？第二，在转运过程中，是什么因素触发了转运蛋白的构象变化？使用基于结构的研究手段对次级主动运输蛋白进行研究，以期解决转运蛋白工作机理中的基本问题。
Abstract：
Voltage-gated sodium (Nav) channels are essential for the rapid depolarization of nerve and muscle, and are important drug targets. Elucidation of the structures and functional mechanisms of Nav channels will shed light on fundamental ion channel mechanisms and facilitate potential clinical applications. A family of bacterial Nav channels, exemplified by NaChBac (Na+-selective Channel of Bacteria), provides a good model system for structure-function analysis. Here we report the crystal structure of NavAP, a NaChBac orthologue from marine bacteria alpha proteobacterium HIMB114, at 3.05 Å resolution. The channel comprises an asymmetric tetramer. The carbonyl oxygen atoms of Thr178 and Leu179 constitute an inner site within the selectivity filter (178TLSSWE183) where a hydrated Ca2+ can bind and resides in the crystal structure. The outer mouth of the Na+ selectivity filter, defined by Ser181 and Glu183, is closed, as is the activation gate at the intracellular side of the pore. The voltage sensors adopt a depolarized conformation with all the gating charges exposing to the extracellular side. We hypothesize that NavAP is captured in an inactivated conformation. Comparison of NavAP with NavAb reveals significant conformational rearrangements that may underlie the electromechanical coupling mechanism of voltage-gated channels.
Selected Publications:
1. Xu Zhang, Wenlin Ren, Paul DeCaen, Chuangye Yan, Xiao Tao, Lin Tang, Jingjing Wang, Kazuya Hasegawa, Takashi Kumasaka, JianhuaHe, Jiawei Wang, David E. Clapham, and Nieng Yan (2012). Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel. Nature, 486: 130-134 (Epub 2012 May 20)
2.Dong Deng, Chuangye Yan, Xiaojing Pan, Magdy Mahfouz, Jiawei Wang, Jian-Kang Zhu, Yigong Shi#, and Nieng Yan# (2012) Structural basis for the specific recognition of DNA by TAL effectors. Science, 335: 720-3 [Epub 2012 Jan 5] (# indicates corresponding authors).
3.Feiran Lu, Shuo Li, Yang Jiang, Jing Jiang, He Fan, Guifeng Lu, Dong Deng, Shangyu Dang, Xu Zhang, Jiawei Wang, and Nieng Yan. (2011) Structure and mechanism of the uracil transporter UraA. Nature, 473: 243-6 (Epub 2011 Mar 20).
4.Shangyu Dang, Linfeng Sun, Feiran Lu, Jiawei Wang, and Nieng Yan. (2010) The structure of a fucose transporter in an outward-open conformation. Nature, 467: 734-8
5.Shiqian Qi, Yuxuan Pang, Qun Liu, Hua Li, Yexing Liu, Quan Hao, Huilin Li, Nieng Yan#, and Yigong Shi# (2009) Structure of the CED-4 Apoptosome: Insights into its Assembly and Function. Cell, 141:446-457 (# indicates corresponding authors).
6.Yi Wang, Yongjian Huang, Jiawei Wang, Chao Cheng, Weijiao Huang, Peilong Lu, Ya-Nan Xu, Pengye Wang, Nieng Yan#, and Yigong Shi#. (2009) Structure of the formate transporter FocA reveals a pentameric aquaporin-like channel. Nature (article) 462: 467-472 (# indicates corresponding authors)
7.Nieng Yan# and Yigong Shi# (2007) Allosteric activation of a bacterial stress sensor. (Preview) Cell, 131:441-443. (# indicates corresponding authors.)
8. Liang Feng, Huanchi Yan, Zhuoru Wu, Nieng Yan, Zhe Wang, Philip D Jeffrey, and Yigong Shi (2007).Structure of a Site-2 Protease Family Intramembrane Metalloprotease. Science, 318: 1608-1612
9.Nieng
10.Liang Feng, David A. Gell, Suiping Zhou,
