以多維核磁共振探討纖維母細胞生長因子與接受子的結合結構及肝素在活化機制所扮演的角色

The NMR Studies of the Complex Structure of Acidic Fibroblast Growth Factor and Its Receptor D2 Domain by Using NMR: Role of Heparinin the Activation of the Receptor

余靖(Chin Yu)

《化學》 66卷3期 (2008/09) Pp. 177-189

https://doi.org/10.6623/chem.2008018

摘要

纖維母細胞生長因子與其細胞表面的接受子結合所產生的細胞訊息傳遞涉及了相當廣泛的生物活性，包括了：胚胎的發展、器官的形成、細胞的分化、增生、遷移、存活、凋亡等。甚至癌細胞的異常增生也被發現和其訊息控調異常有關。然而，對於纖維母細胞生長因子與其接受子的結合而啟動訊息傳遞的機制卻常因為研究方法不同而有不同的解釋。在本篇論文中，我們將利用核磁共振技術，從蛋白質相互作用時的結構變化來探討纖維母細胞生長因子及接受子啟動細胞訊息傳遞的機制，並透過與X-ray晶體技術解析出的結構比較，希望能從結構上了解蛋白質之間的結合是如何啟動蛋白質的活性，更希望能對纖維母細胞生長因子有更進一步的了解。

關鍵字

纖維母細胞生長因子 ； 纖維母細胞生長因子接受子 ； 細胞訊息傳遞 ； 核磁共振

並列摘要

Celluar signaling transduced by the binding of fibroblast growth factor (FGFs) and its receptors (FGFRs) is considered to be involved in the stimulation of a variety of biological and physiological activities, including embryonic development, morphogenesis, cell differentiation, proliferation, migration, and apoptosis. Additionally, the extraordinarily fast proliferation and lose of apoptosis ability of tumor cells is also attributed to the ill-regulation of FGF/FGFR signals. Yet, models of the mechanism as to how the combination of FGF/FGFR triggers signal cascade are diversified owing to the inherent limits of the techniques that are used. Here, we use multidimensional nuclear magnetic resonance (NMR) technique to investigate the structural events involving in the FGF/FGFR interactions, and to compare the observations with that which obtained from X-ray crystallography, hoping to attain the information of which proteins originate the signal cascade by interacting to its counterpart in the view of structure-function relationship.

並列關鍵字

Fibroblast growth factor ； Fibroblast growth factor receptor ； Cellular signal cascade ； Nuclear magnetic resonance ； NMR