Porta Jason C, Han Bing, Gulsevin Alican, Chung Jeong Min, Peskova Yelena, Connolly Sarah, Mchaourab Hassane S, Meiler Jens, Karakas Erkan, Kenworthy Anne K, Ohi Melanie D
Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
Center for Membrane and Cell Physiology, University of Virginia, Charlottesville, VA, USA.
Sci Adv. 2022 May 13;8(19):eabn7232. doi: 10.1126/sciadv.abn7232. Epub 2022 May 11.
Membrane-sculpting proteins shape the morphology of cell membranes and facilitate remodeling in response to physiological and environmental cues. Complexes of the monotopic membrane protein caveolin function as essential curvature-generating components of caveolae, flask-shaped invaginations that sense and respond to plasma membrane tension. However, the structural basis for caveolin's membrane remodeling activity is currently unknown. Here, we show that, using cryo-electron microscopy, the human caveolin-1 complex is composed of 11 protomers organized into a tightly packed disc with a flat membrane-embedded surface. The structural insights suggest a previously unrecognized mechanism for how membrane-sculpting proteins interact with membranes and reveal how key regions of caveolin-1, including its scaffolding, oligomerization, and intramembrane domains, contribute to its function.
膜塑形蛋白塑造细胞膜的形态，并促进其响应生理和环境信号进行重塑。单拓扑膜蛋白小窝蛋白形成的复合物是小窝（烧瓶状内陷结构，可感知质膜张力并作出响应）中产生曲率的关键成分。然而，目前尚不清楚小窝蛋白膜重塑活性的结构基础。在这里，我们通过冷冻电子显微镜显示，人源小窝蛋白-1复合物由11个原体组成，这些原体组装成一个紧密堆积的盘状结构，其膜嵌入表面呈扁平状。这些结构见解揭示了一种此前未被认识的膜塑形蛋白与膜相互作用的机制，并揭示了小窝蛋白-1的关键区域（包括其支架结构域、寡聚化结构域和膜内结构域）是如何发挥其功能的。
