Im Young Jun, Wollert Thomas, Boura Evzen, Hurley James H
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD 20892, USA.
Dev Cell. 2009 Aug;17(2):234-43. doi: 10.1016/j.devcel.2009.07.008.
The ESCRT-II-ESCRT-III interaction coordinates the sorting of ubiquitinated cargo with the budding and scission of intralumenal vesicles into multivesicular bodies. The interacting regions of these complexes were mapped to the second winged helix domain of human ESCRT-II subunit VPS25 and the first helix of ESCRT-III subunit VPS20. The crystal structure of this complex was determined at 2.0 A resolution. Residues involved in structural interactions explain the specificity of ESCRT-II for Vps20, and are critical for cargo sorting in vivo. ESCRT-II directly activates ESCRT-III-driven vesicle budding and scission in vitro via these structural interactions. VPS20 and ESCRT-II bind membranes with nanomolar affinity, explaining why binding to ESCRT-II is dispensable for the recruitment of Vps20 to membranes. Docking of the ESCRT-II-VPS20(2) supercomplex reveals a convex membrane-binding surface, suggesting a hypothesis for negative membrane curvature induction in the nascent intralumenal vesicle.
ESCRT-II与ESCRT-III的相互作用协调了泛素化货物的分选与腔内小泡出芽并切割形成多囊泡体的过程。这些复合物的相互作用区域被定位到人类ESCRT-II亚基VPS25的第二个翼状螺旋结构域和ESCRT-III亚基VPS20的第一个螺旋结构域。该复合物的晶体结构在2.0埃分辨率下得以确定。参与结构相互作用的残基解释了ESCRT-II对Vps20的特异性，并且对体内货物分选至关重要。在体外，ESCRT-II通过这些结构相互作用直接激活ESCRT-III驱动的小泡出芽和切割。VPS20和ESCRT-II以纳摩尔亲和力结合膜，这解释了为何Vps20募集到膜上时与ESCRT-II的结合并非必需。ESCRT-II-VPS20(2)超复合物的对接揭示了一个凸面的膜结合表面，这为新生腔内小泡中负膜曲率的诱导提出了一个假说。
