Abstract：
GPCRs receive signals from diverse messengers and activate G proteins that regulate downstream signaling effectors. Efficient signaling is achieved through the organization of these proteins in membranes. Thus, protein-lipid interactions play a critical role in bringing G proteins together in specific membrane microdomains with signaling partners. Significantly, the molecular basis underlying the membrane distribution of each G protein isoform, fundamental to fully understanding subsequent cell signaling, remains largely unclear. We used model membranes with lipid composition resembling different membrane microdomains, and monomeric, dimeric and trimeric Gi proteins with or without single and multiple mutations to investigate the structural bases of G protein-membrane interactions. We demonstrated that cationic amino acids in the N-terminal region of the Gαi1 and C-terminal region of the Gγ2 subunit, as well as their myristoyl, palmitoyl and geranylgeranyl moieties, define the differential G protein form interactions with membranes containing different lipid classes (PC, PS, PE, SM, Cho) and the various microdomains they may form (Lo, Ld, PC bilayer, charged, etc.). These new findings in part explain the molecular basis underlying amphitropic protein translocation to membranes and localization to different membrane microdomains and the role of these interactions in cell signal propagation, pathophysiology and therapies targeted to lipid membranes.
摘要：
GPCR接收来自不同信使的信号并激活调节下游信号效应物的G蛋白。通过这些蛋白质在膜中的组织实现有效的信号传导。因此，蛋白质-脂质相互作用在将G蛋白与信号伙伴一起聚集在特定膜微结构域中起关键作用。重要的是,每个G蛋白同种型的膜分布的分子基础，完全理解后续细胞信号的基础，基本上还不清楚。我们使用了脂质组成类似于不同膜微域的模型膜，和单体，具有或不具有单个和多个突变的二聚体和三聚体Gi蛋白，以研究G蛋白-膜相互作用的结构基础。我们证明了Gαi1的N末端区域和Gγ2亚基的C末端区域中的阳离子氨基酸，以及他们的肉豆蔻酰基，棕榈酰基和香叶基香叶酰基部分，定义与含有不同脂质类别的膜的差异G蛋白形式相互作用(PC，PS,PE,SM,Cho)和它们可能形成的各种微域(Lo，Ld,PC双层,收费，等。).这些新发现部分解释了两性蛋白质易位到膜和定位到不同膜微结构域的分子基础，以及这些相互作用在细胞信号传播中的作用。病理生理学和针对脂质膜的治疗。
