Cargo selectivity of the mammalian COPII coat complex

描述（由申请人提供）：真核细胞的一个标志是细胞功能在膜封闭细胞器内的区隔化。小的（直径50-100纳米）囊泡在细胞器之间运输选定的货物蛋白质和脂质分子。选择性转运确保细胞器组成的维持，是关键细胞过程的潜在机制，如内吞作用、分泌功能、激素和神经递质的胞吐。COPII外壳复合体通过将新合成的蛋白质整合到从内质网（ER）产生的囊泡中并与早期高尔基区室融合，介导了分泌交通的第一步。目前的建议旨在利用生物化学和x射线晶体学方法的组合研究哺乳动物COPII复合体的货物选择的分子决定因素。具体而言，该提案旨在研究生物学上重要的哺乳动物货物分子，包括：分泌生长因子，SNAREs，细胞表面受体和膜通道。最终目的是提供所有哺乳动物内质网输出基序及其与COPII外壳复合物相互作用的分子水平描述。

DESCRIPTION (provided by applicant): A hallmark of eukaryotic cells is the compartmentalization of cellular functions within membrane-enclosed organelles. Small (50-100 nm diameter) vesicles traffic between organelles transporting select cargo protein and lipid molecules. Selective transport ensures the maintenance of the organelle composition and is the underlying mechanism of key cellular processes such as endocytosis, secretory function, and exocytosis of hormones and neurotransmitters. The COPII coat complex mediates the first step in secretory traffic by incorporating newly synthesized proteins into vesicles that bud from the endoplasmic reticulum (ER) and fuse with early Golgi compartments. The current proposal seeks to study the molecular determinants of cargo selection by the mammalian COPII complex using a combination of biochemical and X-ray crystallographic methods. Specifically, the proposal aims to study biologically important mammalian cargo molecules including: secreted growth factors, SNAREs, cell surface receptors, and membrane channels. The ultimate aim is to provide a molecular level description of all mammalian ER export motifs and their interaction with the COPII coat complex.