Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02124, USA.
Department of Chemistry, James Franck Institute, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
Dev Cell. 2018 Jan 8;44(1):73-86.e4. doi: 10.1016/j.devcel.2017.12.011.
Cytosolic lipid droplets (LDs) are the main storage organelles for metabolic energy in most cells. They are unusual organelles that are bounded by a phospholipid monolayer and specific surface proteins, including key enzymes of lipid and energy metabolism. Proteins targeting LDs from the cytoplasm often contain amphipathic helices, but how they bind to LDs is not well understood. Combining computer simulations with experimental studies in vitro and in cells, we uncover a general mechanism for targeting of cytosolic proteins to LDs: large hydrophobic residues of amphipathic helices detect and bind to large, persistent membrane packing defects that are unique to the LD surface. Surprisingly, amphipathic helices with large hydrophobic residues from many different proteins are capable of binding to LDs. This suggests that LD protein composition is additionally determined by mechanisms that selectively prevent proteins from binding LDs, such as macromolecular crowding at the LD surface.
细胞质脂滴（LDs）是大多数细胞中代谢能量的主要储存细胞器。它们是一种特殊的细胞器，由一个磷脂双层和特定的表面蛋白所限定，其中包括脂质和能量代谢的关键酶。从细胞质靶向 LDs 的蛋白质通常含有两亲性螺旋，但它们与 LDs 的结合方式尚不清楚。我们将计算机模拟与体外和细胞内的实验研究相结合，揭示了一种将细胞质蛋白靶向 LDs 的一般机制：两亲性螺旋的大疏水性残基可检测并结合到 LD 表面特有的大的、持久的膜堆积缺陷。令人惊讶的是，来自许多不同蛋白质的具有大疏水性残基的两亲性螺旋都能够与 LDs 结合。这表明 LD 的蛋白质组成还取决于选择性地防止蛋白质与 LDs 结合的机制，例如 LD 表面的大分子拥挤。
