MAMMALIAN COG4

哺乳动物COG4

• 批准号: 7957255
• 负责人: FREDERICK M HUGHSON
• 金额: $ 0.79万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7957255
• 关键词: Affect; Architecture; Area; Cell Surface Proteins; Complex; Computer Retrieval of Information on Scientific Projects Database; Crystallography; Data; Data Collection; Defect; Funding; Goals; Golgi Apparatus; Grant; Image; Institution; L-Selenomethionine; Laboratories; Light; Membrane; Molecular; Pathway interactions; Phase; Play; Proteins; Publishing; Research; Research Personnel; Resources; Role; Science; Sorting - Cell Movement; Source; Structure; Synchrotrons; United States National Institutes of Health; Vesicle; Work; Writing; detector; glycosylation; human disease; meetings; trafficking

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 Golgi apparatus plays a key role in protein sorting and glycoslyation within the eukaryotic secretory pathway. Defects in vesicular trafficking within the Golgi affect both its structure and function. As a consequence, such defects can have pleiotropic effects on the glycosylation and stability of cell surface proteins, leading to human disease. This proposal arises from work funded by the NIH (RO1 GM071574: "Structural Analysis of Golgi Tethering Proteins"). Our efforts in this area, generally speaking, are focused on two large complexes, the Conserved Oligomeric Golgi (COG) complex and the Dsl1 complex. Both are essential for intracellular trafficking and are thought to act in the initial tethering of intracellular trafficking vesicles to their membrane targets. Nonetheless, despite intensive efforts, little is known about the molecular mechanism by which these complexes function in vesicle tethering. Our long-term goal is to determine crystal structures of subunits and subassemblies of the COG (8 subunits) and Dsl1 (4 subunits) complexes. We have done extensive preliminary work, especially with COG, in characterizing the overall architecture (i.e. subunit connectivity) of the complex. There are, however, no published structures of any portion of either complex. We have recently obtained promising crystals of subunits of each complex, and propose to determine their structures at NSLS using MAD phasing. Here, we write to request X-25 or X-29 beamtime to determine the structure of a fragment of mammalian Cog4. We call this 265-residue fragment Cog4B. Our current Cog4B crystals diffract x-rays well, to at least 3.0 angstroms using our laboratory's R-Axis IV image plate detector. Therefore, current efforts are focused on obtaining SeMet-substituted crystals for MAD data collection. Since the total number of Met residues is low for a protein of this size (4 Met over 265 residues), high-quality synchrotron data is likely to be instrumental for MAD phasing. Given the importance of the science and the promise of the preliminary data, we feel it is vital to collect data as soon as possible.

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