期刊
SCIENCE ADVANCES
卷 8, 期 44, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abo5295
关键词
-
资金
- Novo Nordisk Foundation Challenge Program under the Center for Geometrically Engineered Cellular Systems
- NIH [PO1 A1091580]
- NSF, Division of Chemistry award [CHE1954580]
LAT protein undergoes a phase transition to form a two-dimensional protein condensate on the membrane during T cell activation. The condensation process is kinetically frustrated by the availability of bonds to form the percolation network. The results reveal the structural basis and local factors controlling the kinetics of LAT condensation.
LAT is a membrane-linked scaffold protein that undergoes a phase transition to form a two-dimensional protein condensate on the membrane during T cell activation. Governed by tyrosine phosphorylation, LAT recruits various proteins that ultimately enable condensation through a percolation network of discrete and selective protein-protein interactions. Here, we describe detailed kinetic measurements of the phase transition, along with coarse-grained model simulations, that reveal that LAT condensation is kinetically frustrated by the availability of bonds to form the network. Unlike typical miscibility transitions in which compact domains may coexist at equilibrium, the LAT condensates are dynamically arrested in extended states, kinetically trapped out of equilibrium. Modeling identifies the structural basis for this kinetic arrest as the formation of spindle arrangements, favored by limited multivalent binding interactions along the flexible, intrinsically disordered LAT protein. These results reveal how local factors controlling the kinetics of LAT condensation enable formation of different, stable condensates, which may ultimately coexist within the cell.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据