转运必需内体分选复合物(endosomal sorting complex required for transport,ESCRT)系统是真核细胞中完成内体(endosome)膜内陷以形成多囊泡体(multi-vesicular body,MVB)的分子机器,其主要功能是促进被泛素(ubiquitin)标记的膜蛋白的降解,还与细胞分裂、病毒出芽、细胞自噬以及真菌pH感知相关.ESCRT系统包括ESCRT-0,-I,-Ⅱ,一Ⅲ和Vps4-Vtal共5个蛋白.蛋白复合物.晶体学研究已经解析了大部分复合物的结构.其促使膜内陷的分子机理一般认为分3步.首先是ESCRT-I和-Ⅱ在内体膜上结合并促使内体膜内陷形成初始芽体.之后,ESCRT-Ⅲ在芽体颈部聚合并导致芽体的剪切,从而将内腔囊泡(intralumenal vesicles,ILVs)释放到内体腔内,形成MVB.最后,Vps4/Vtal复合物则以水解ATP提供能量将聚合的ESCRT-Ⅲ解聚以循环使用,完成更多的出芽过程.本文将对ESCRT系统的结构、出芽机理和生物功能几方面做一个综述.
The endosomal sorting complex required for transport (ESCRT) system is essential for the degradation of ubiquitinated membrane proteins and comprises a major pathway for MVB (multi-vesicular body) formation. ESCRT is also involved in retrovirus budding, cell division, autophagy and fungi pH sensing. Five protein complexes were identified in the ESCR system: ESCRT-0, - I , -Ⅱ , -Ⅲ and Vps4-Vtal. ESCRT-I and -Ⅱ induce the formation of the initial bud during the budding process. ESCRT-Ⅲ forms a lattice at the endosomal membrane and completes the scission at the bud neck, and Vps4-Vtal complex finally disassembles the ESCRT-Ⅲ lattice to recycle ESCRT machinery components. This review summarizes the structural features, budding mechanism and biological roles of the ESCRT system.