Schlebach Jonathan P, Barrett Paul J, Day Charles A, Kim Ji Hun, Kenworthy Anne K, Sanders Charles R
Department of Biochemistry, ‡Center for Structural Biology, §Department of Molecular Physiology and Biophysics, ∥Department of Cell and Developmental Biology, Vanderbilt University School of Medicine , Nashville, Tennessee 37240, United States.
Biochemistry. 2016 Feb 23;55(7):985-8. doi: 10.1021/acs.biochem.5b01154. Epub 2016 Feb 11.
The integration of membrane proteins into "lipid raft" membrane domains influences many biochemical processes. The intrinsic structural properties of membrane proteins are thought to mediate their partitioning between membrane domains. However, whether membrane topology influences the targeting of proteins to rafts remains unclear. To address this question, we examined the domain preference of three putative raft-associated membrane proteins with widely different topologies: human caveolin-3, C99 (the 99 residue C-terminal domain of the amyloid precursor protein), and peripheral myelin protein 22. We find that each of these proteins are excluded from the ordered domains of giant unilamellar vesicles containing coexisting liquid-ordered and liquid-disordered phases. Thus, the intrinsic structural properties of these three topologically distinct disease-linked proteins are insufficient to confer affinity for synthetic raft-like domains.
膜蛋白整合到“脂筏”膜结构域中会影响许多生化过程。膜蛋白的固有结构特性被认为介导了它们在膜结构域之间的分配。然而，膜拓扑结构是否影响蛋白质靶向脂筏仍不清楚。为了解决这个问题，我们研究了三种拓扑结构差异很大的假定脂筏相关膜蛋白的结构域偏好：人小窝蛋白-3、C99（淀粉样前体蛋白的99个残基C末端结构域）和外周髓鞘蛋白22。我们发现，这些蛋白质中的每一种都被排除在含有共存的液相有序和液相无序相的巨型单层囊泡的有序结构域之外。因此，这三种拓扑结构不同的疾病相关蛋白的固有结构特性不足以赋予它们对合成脂筏样结构域的亲和力。
