Cargo selectivity of the mammalian COPII coat complex

哺乳动物 COPII 外套复合物的货物选择性

• 批准号: 7123783
• 负责人: Joseph D Mancias
• 金额: $ 4.13万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-03 至 2007-09-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7123783
• 关键词: Golgi apparatus; NMDA receptors; X ray crystallography; cell component structure /function; chemokine receptor; endoplasmic reticulum; glycoproteins; potassium channel; predoctoral investigator; protein binding; protein protein interaction; protein structure function; secretion; secretory protein

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.

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的细胞器内的划分。小（直径 50-100 nm）囊泡在细胞器之间运输，运输选定的货物蛋白和脂质分子。选择性运输确保细胞器组成的维持，并且是关键细胞过程（例如激素和神经递质的内吞作用、分泌功能以及胞吐作用）的基本机制。 COPII 外壳复合物通过将新合成的蛋白质掺入从内质网 (ER) 出芽并与早期高尔基体区室融合的囊泡中来介导分泌运输的第一步。目前的提案旨在结合生化和 X 射线晶体学方法，研究哺乳动物 COPII 复合物选择货物的分子决定因素。具体来说，该提案旨在研究生物学上重要的哺乳动物货物分子，包括：分泌的生长因子、SNARE、细胞表面受体和膜通道。最终目标是提供所有哺乳动物 ER 输出基序及其与 COPII 外壳复合物相互作用的分子水平描述。