CRYSTALLOGRAPHIC STUDIES ON NUCLEAR PORE COMPLEX PROTEINS

核孔复合蛋白的晶体学研究

• 批准号: 7721244
• 负责人: GUNTER BLOBEL
• 金额: $ 1.41万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-15 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721244
• 关键词: Active Biological Transport; Cellular biology; Chromatin; Complex; Computer Retrieval of Information on Scientific Projects Database; Cytoplasm; Cytoplasmic Filaments; Diffusion; Eukaryotic Cell; Exhibits; Funding; Gene Expression; Goals; Grant; Institution; Kinetochores; Macromolecular Complexes; Mitosis; Names; Nuclear Envelope; Nuclear Pore; Nuclear Pore Complex; Nuclear Pore Complex Proteins; Nucleoplasm; Proteins; Research; Research Personnel; Resources; Role; Running; Side; Source; Structure; United States National Institutes of Health; Vertebrates; X-Ray Crystallography; Yeasts; insight; nuclear pore complex protein 96; nuclear pore complex protein p107; three dimensional structure; tumorigenesis

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The nuclear pore complex (NPC) is one of the largest macromolecular complexes in the eukaryotic cell (approximately 60 MDa and 125 MDa in yeast and vertebrates, respectively), composed of about 30 different interacting proteins named as nucleoporins. The nuclear pore exhibits an octagonal symmetry around its cylindrical axis. It consists of a cylindrical core, composed of eight interconnected spokes. Each spoke is composed of the Nup93, Nup205 and Nup188 nucleoporins, and surrounds the central channel. These spokes are further connected on the nucleoplasm and cytoplasm sides to a Nup160 subcomplex (Nup133, Nup96, Nup107, Nup37, Nup43, Nup160, Nup75). The Nup160 complex hence forms a plane pseudo-mirror symmetry running parallel to the nuclear envelope. The central ring of NPC is further connected to 50-100 nm long fibrils extended either into the nucleoplasm (to form basket like structure) or into cytoplasm as cytoplasmic filaments. The role of such intricate NPC assembly in eukaryotic cell biology is very diverse and mainly includes: nucleo-cytoplasmic transport by either diffusion or active transport, organization of perinuclear chromatin, interactions with kinetochores during mitosis, control of gene expression, oncogenesis etc. However, how these functions are controlled/regulated by NPC assembly is not fully understood. The studies in our lab are focused to gain the structural insights into the mechanism of NPC assembly. The major goal of the project is to crystallize these nucleoporins either individually or in complex with their partners and determine its 3D structure using X-ray crystallography. These studies will help us to visualize the mechanistic details of NPC assembly and might be able to postulate hypothesis for versatile role of the NPC.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 核孔复合物（nuclear pore complex，NPC）是真核细胞中最大的大分子复合物之一（酵母和脊椎动物中分别约为60 MDa和125 MDa），由约30种不同的相互作用蛋白质组成，称为核孔蛋白。核孔呈八边形对称。它由一个圆柱形的核心，由八个相互连接的辐条组成。每个轮辐由Nup93、Nup205和Nup188核孔蛋白组成，并围绕中央通道。 这些辐条在核质和细胞质侧进一步连接到Nup160亚复合体（Nup133、Nup96、Nup107、Nup37、Nup43、Nup160、Nup75）。Nup160复合物因此形成平行于核膜的平面伪镜像对称。NPC的中心环进一步连接到50 - 100 nm长的纤维，该纤维延伸到核质中（以形成篮状结构）或作为细胞质丝延伸到细胞质中。这种复杂的NPC组装在真核细胞生物学中的作用是非常多样的，主要包括：通过扩散或主动运输的核质运输，核周染色质的组织，有丝分裂过程中与动粒的相互作用，基因表达的控制，肿瘤发生等。我们实验室的研究主要集中在对NPC组装机制的结构理解上。该项目的主要目标是将这些核孔蛋白单独或与其伙伴复合结晶，并使用X射线晶体学确定其3D结构。这些研究将有助于我们可视化NPC组装的机制细节，并可能能够假设NPC的多功能作用。