Membrane contact sites between organelles are organized by protein bridges. Among the components of these contacts, the VAP family comprises ER–anchored proteins, such as MOSPD2, that function as major ER–organelle tethers. MOSPD2 distinguishes itself from the other members of the VAP family by the presence of a CRAL-TRIO domain. In this study, we show that MOSPD2 forms ER–lipid droplet (LD) contacts, thanks to its CRAL-TRIO domain. MOSPD2 ensures the attachment of the ER to LDs through a direct protein–membrane interaction. The attachment mechanism involves an amphipathic helix that has an affinity for lipid packing defects present at the surface of LDs. Remarkably, the absence of MOSPD2 markedly disturbs the assembly of lipid droplets. These data show that MOSPD2, in addition to being a general ER receptor for inter-organelle contacts, possesses an additional tethering activity and is specifically implicated in the biology of LDs via its CRAL-TRIO domain.

中文翻译：

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MOSPD2 是一种内质网-脂滴系链，在 LD 稳态中发挥作用


细胞器之间的膜接触位点由蛋白质桥组织。在这些接触的组成部分中，VAP 家族包括 ER 锚定蛋白，例如 MOSPD2，其充当主要的 ER 细胞器系链。 MOSPD2 与 VAP 家族其他成员的区别在于 CRAL-TRIO 结构域的存在。在这项研究中，我们发现 MOSPD2 凭借其 CRAL-TRIO 结构域形成 ER-脂滴 (LD) 接触。 MOSPD2 通过直接的蛋白质-膜相互作用确保 ER 与 LD 的连接。附着机制涉及两亲螺旋，该螺旋对 LD 表面存在的脂质堆积缺陷具有亲和力。值得注意的是，MOSPD2 的缺失会显着扰乱脂滴的组装。这些数据表明，MOSPD2 除了作为细胞器间接触的通用 ER 受体外，还具有额外的束缚活性，并且通过其 CRAL-TRIO 结构域与 LD 的生物学有明确关系。