GAP JUNCTION

间隙连接

• 批准号: 7598626
• 负责人: GINA E SOSINSKY
• 金额: $ 0.81万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7598626
• 关键词: Animals; Class; Computer Retrieval of Information on Scientific Projects Database; Connexins; Crystallization; Data; Databases; Detergents; Development; Disease; Electrons; Funding; Gap Junctions; Grant; Hybrids; Institution; Membrane; Methods; Procedures; Range; Research; Research Personnel; Resolution; Resources; Source; Specimen; Structure; United States National Institutes of Health; image processing; interest; mutant; particle; reconstruction; three dimensional structure

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. Gap junctions (GJs) represent a ubiquitous component of all multicellular animals, and GJ s were one of the first specimens examined by electron crystallographic methods. However, the majority (99.9%) of these crystals have good short range order combined with long range disorder that results in coherent diffraction data generally only to about ~15-25 ¿. As a result, there is only one 3D structure obtained at > 10 ¿ (Unger et al., 1999). This is an important point because one of the aims is to reinvent image processing procedures that would allow us to obtain structural data based on a hybrid crystallographic/single particle reconstruction approach for greater throughput. Furthermore, we have found that there are classes of interesting connexin functional mutants where the hexamer or dodecamer is stable when held within the membrane, but dissociates upon detergent solubilization. For these mutants, crystallization for a high resolution structure will never be possible. We began development of hybrid methods of image processing combining crystallographic information with single particle reconstruction methods so it is much less dependent on lattice order.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 缝隙连接(GJS)代表了所有多细胞动物中普遍存在的成分，并且 GJ S是最早用电子结晶学方法检验的标本之一。然而，大多数晶体(99.9%)具有良好的短程有序性和长程无序，导致相干衍射数据一般只有15-25？因此，在&gt；10？上只获得了一种3D结构(Unger等人，1999年)。这一点很重要，因为目标之一是重新发明图像处理程序，使我们能够基于混合晶体/单粒子重建方法获得结构数据，以获得更大的吞吐量。此外，我们发现有一些有趣的连接蛋白功能突变体，其中六聚体或十二聚体在膜内保持稳定，但在洗涤剂溶解时解离。对于这些突变体来说，高分辨率结构的结晶永远不可能实现。我们开始开发混合的图像处理方法，将结晶学信息与单粒子重建方法相结合，因此它对晶格顺序的依赖要小得多。