Department of Biochemistry and Biophysics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Structure. 2012 Jan 11;20(1):15-27. doi: 10.1016/j.str.2011.11.012. Epub 2011 Dec 21.
Regulated relocalization of signaling and trafficking proteins is crucial for the control of many cellular processes and is driven by a series of domains that respond to alterations at membrane surfaces. The first examples of these domains--conditional peripheral membrane proteins--included C1, C2, PH, PX, and FYVE domains, which specifically recognize single tightly regulated membrane components such as diacylglycerol or phosphoinositides. The structural basis for this recognition is now well understood. Efforts to identify additional domains with similar functions that bind other targets (or participate in unexplained cellular processes) have not yielded many more examples of specific phospholipid-binding domains. Instead, most of the recently discovered conditional peripheral membrane proteins bind multiple targets (each with limited specificity), relying on coincidence detection and/or recognizing broader physical properties of the membrane such as charge or curvature. This broader range of recognition modes presents significant methodological challenges for a full structural understanding.
信号和运输蛋白的调控再定位对于许多细胞过程的控制至关重要，这是由一系列响应膜表面变化的结构域驱动的。这些结构域中的第一批例子——条件外周膜蛋白——包括 C1、C2、PH、PX 和 FYVE 结构域，它们专门识别单一的、受到严格调控的膜成分，如二酰基甘油或磷酸肌醇。现在已经很好地理解了这种识别的结构基础。然而，为了识别具有类似功能的其他结构域，以结合其他靶标（或参与未解释的细胞过程），并没有产生更多特定的磷脂结合结构域的例子。相反，最近发现的大多数条件外周膜蛋白结合多个靶标（每个靶标都有有限的特异性），依赖于巧合检测和/或识别膜的更广泛物理特性，如电荷或曲率。这种更广泛的识别模式给全面的结构理解带来了重大的方法学挑战。
