Understanding cell signalling systems: paving the way for new therapies.
Understanding cell signalling systems: paving the way for new therapies.
复制标题
DOI：
10.1098/rsta.2013.0155
复制
发表时间：
2015-03-06
期刊：
影响因子：
--
通讯作者：
Jones EY
中科院分区：
文献类型：
--
作者：
Jones EY
多细胞生物的细胞间信号传导机制在胚胎发生过程中协调人类发育并控制成体组织的稳态。这些机制对人类健康至关重要，细胞间信号传导的扰动是包括癌症在内的许多病理学的影响因素。信号蛋白细胞引导信号及其同源丛蛋白受体例证了细胞间信号传导系统，其机制原理的见解正在出现。来自金刚石光束线的 X 射线晶体学数据使我们能够以原子级分辨率探测信号蛋白-丛蛋白信号传导的内部工作原理。重要的是，我们可以通过生物物理和细胞研究来补充蛋白质晶体学结果，使结构信息与功能影响相吻合。信号蛋白的标志性七叶β螺旋桨“sema”结构域形成二聚体；相反，丛蛋白中的等效结构域是单体的。信号蛋白-丛蛋白复合物的通用结构的特征是二聚体信号蛋白交联两个丛蛋白受体拷贝。对于特定的家族成员，共受体神经毡蛋白可以增强这种结构，但在所有情况下，二聚体相互作用都位于配体受体复合物的核心，为信号传导提供了必要的触发因素。
The cell-to-cell signalling mechanisms of multi-cellular organisms orchestrate human development during embryogenesis and control homeostasis in adult tissues. These are mechanisms vital to human health and perturbation of cell-to-cell signalling is a contributing factor in many pathologies including cancer. The semaphorin cell guidance cues and their cognate plexin receptors exemplify a cell-to-cell signalling system for which insights into mechanistic principles are emerging. X-ray crystallographic data from Diamond beam lines have enabled us to probe the inner workings of semaphorin–plexin signalling to atomic-level resolutions. Importantly, we can complement protein crystallographic results with biophysical and cellular studies to dovetail structural information with functional impact. The signature seven-bladed β propeller ‘sema’ domain of the semaphorins forms a dimer; in contrast the equivalent domain in the plexins is monomeric. The generic architecture of a semaphorin–plexin complex is characterized by the dimeric semaphorin cross-linking two copies of the plexin receptor. For specific family members, the co-receptor neuropilin serves to bolster this architecture, but in all cases, the dimeric interaction lies at the core of the ligand receptor complex, providing the essential trigger for signalling.
登录
查看更多内容
影响因子：
9.8
作者：
Bell CH;Aricescu AR;Jones EY;Siebold C
通讯作者：
Siebold C
影响因子：
64.8
作者：
Biankin, Andrew V.;Waddell, Nicola;Kassahn, Karin S.;Gingras, Marie-Claude;Muthuswamy, Lakshmi B.;Johns, Amber L.;Miller, David K.;Wilson, Peter J.;Patch, Ann-Marie;Wu, Jianmin;Chang, David K.;Cowley, Mark J.;Gardiner, Brooke B.;Song, Sarah;Harliwong, Ivon;Idrisoglu, Senel;Nourse, Craig;Nourbakhsh, Ehsan;Manning, Suzanne;Wani, Shivangi;Gongora, Milena;Pajic, Marina;Scarlett, Christopher J.;Gill, Anthony J.;Pinho, Andreia V.;Rooman, Ilse;Anderson, Matthew;Holmes, Oliver;Leonard, Conrad;Taylor, Darrin;Wood, Scott;Xu, Qinying;Nones, Katia;Fink, J. Lynn;Christ, Angelika;Bruxner, Tim;Cloonan, Nicole;Kolle, Gabriel;Newell, Felicity;Pinese, Mark;Mead, R. Scott;Humphris, Jeremy L.;Kaplan, Warren;Jones, Marc D.;Colvin, Emily K.;Nagrial, Adnan M.;Humphrey, Emily S.;Chou, Angela;Chin, Venessa T.;Chantrill, Lorraine A.;Mawson, Amanda;Samra, Jaswinder S.;Kench, James G.;Lovell, Jessica A.;Daly, Roger J.;Merrett, Neil D.;Toon, Christopher;Epari, Krishna;Nguyen, Nam Q.;Barbour, Andrew;Zeps, Nikolajs;Kakkar, Nipun;Zhao, Fengmei;Wu, Yuan Qing;Wang, Min;Muzny, Donna M.;Fisher, William E.;Brunicardi, F. Charles;Hodges, Sally E.;Reid, Jeffrey G.;Drummond, Jennifer;Chang, Kyle;Han, Yi;Lewis, Lora R.;Dinh, Huyen;Buhay, Christian J.;Beck, Timothy;Timms, Lee;Sam, Michelle;Begley, Kimberly;Brown, Andrew;Pai, Deepa;Panchal, Ami;Buchner, Nicholas;De Borja, Richard;Denroche, Robert E.;Yung, Christina K.;Serra, Stefano;Onetto, Nicole;Mukhopadhyay, Debabrata;Tsao, Ming-Sound;Shaw, Patricia A.;Petersen, Gloria M.;Gallinger, Steven;Hruban, Ralph H.;Maitra, Anirban;Iacobuzio-Donahue, Christine A.;Schulick, Richard D.;Wolfgang, Christopher L.;Morgan, Richard A.;Lawlor, Rita T.;Capelli, Paola;Corbo, Vincenzo;Scardoni, Maria;Tortora, Giampaolo;Tempero, Margaret A.;Mann, Karen M.;Jenkins, Nancy A.;Perez-Mancera, Pedro A.;Adams, David J.;Largaespada, David A.;Wessels, Lodewyk F. A.;Rust, Alistair G.;Stein, Lincoln D.;Tuveson, David A.;Copeland, Neal G.;Musgrove, Elizabeth A.;Scarpa, Aldo;Eshleman, James R.;Hudson, Thomas J.;Sutherland, Robert L.;Wheeler, David A.;Pearson, John V.;McPherson, John D.;Gibbs, Richard A.;Grimmond, Sean M.
通讯作者：
Grimmond, Sean M.
影响因子：
64.5
作者：
He, ZG;TessierLavigne, M
通讯作者：
TessierLavigne, M
影响因子：
16.2
作者：
KOLODKIN, AL;MATTHES, DJ;GOODMAN, CS
通讯作者：
GOODMAN, CS
DOI：
10.1107/s0907444906029799
发表时间：
2006-10-01
影响因子：
2.2
作者：
Aricescu, A. Radu;Lu, Weixian;Jones, E. Yvonne
通讯作者：
Jones, E. Yvonne