细胞极性是细胞的基本特性，在细胞分裂、特殊形态形成和执行相关功能时，都起到至关重要的作用。细胞极性的建立和维持通常受到细胞内部极化因子-极性蛋白的调控。HAM-1/STOX1是调控细胞不对称分裂的极性蛋白，主要参与调控神经母细胞不对称分裂过程中细胞极性的建立和维持。研究发现，HAM-1/STOX1含有一个非常保守的N-端结构域（NTD），其可以与PIP脂质直接结合，但是该结构域的自身结构及其与PIP脂质结合的分子机理目前都不清楚。本项目选择HAM-1/STOX NTD为主要研究对象，将综合运用分子生物学、结构生物学以及细胞生物学，对NTD进行结构与功能研究，重点研究其与PIP脂质结合的选择特异性以及相关PIP脂质复合物的结构和功能。通过本项目的研究将揭示HAM-1/STOX1 NTD的结构特征及其结合PIP脂质的分子机制，有利于进一步认识HAM-1/STOX1调控细胞极性建立的功能机理。

Cell polarity is a fundamental property of cells and the polarization of cells is critical for a variety of biological processes, including cell differentiation, proliferation and morphogenesis. The establishment and maintenance of cell polarity are rigorously controlled by intrinsic polarization factors such as polarity proteins. HAM-1/STOX1 is a polarity protein that plays a prominent role in regulating the asymmetric cell division of neuroblasts. HAM-1/STOX1 contains a highly conserved N-terminal domain (NTD), which can directly bind to the PIP lipid membranes. However, the molecular mechanism underlying the recognition of the PIP lipid remains unclear. In this proposal, we focus on the structural studies of the NTD and the mechanism of the PIP lipid recognition. By using molecular biology, structural biology and cell biology, we will work on the binding specificity of the NTD for the PIP lipid and the structural and functional dissection of the NTD/PIP lipid complex. The outcome of this proposal will reveal the molecular mechanism of the PIP lipid recognition of the NTD, which may shed light on the understanding of the fundamental role of HAM-1/STOX1 in controlling cell polarity.