TOWARD THE ATOMIC STRUCTURE OF THE NUCLEAR PORE COMPLEX

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。 在未分裂的细胞中，核孔复合体(NPC)是穿过核膜并到达基因组的唯一通道。因此，对NPC进行原子细节的研究将有助于了解HIV的起始前复合体(PIC)是如何与NPC对接并将其基因组运送到细胞核的。我们的工作成果将取得进步，但并不局限于艾滋病研究的根本方面。 我们的具体目标是确定核孔复合体(NPC)的原子结构，NPC是进入和离开真核细胞核的唯一通道。NPC是一个非常大的大分子组装，大小为40-60个丙二醛。它由大约500个蛋白质分子(核孔蛋白或NUP)组成，围绕中央8倍旋转轴排列成亚复合体。由于许多原因，组装的NPC的结晶是不现实的，我们试图阐明基本结构亚复合体的第一个结构，并在第二步将这些信息与通过单粒子冷冻电子显微镜获得的结构信息相结合。

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 the only passageway across the nuclear envelope and to the genome in a non-dividing cell. As such, investigating the NPC in atomic detail will help understand how the preinitegration complex (PIC) of HIV docks to the NPC and delivers its genome to the nucleus. Results of our work will advance, but it is not limited to, AIDS research in fundamental ways. Our specific aims are to determine the atomic structure of the nuclear pore complex (NPC), the exclusive gateway into and out of the nucleus of the eukaryotic cell. The NPC is a very large macromolecular assembly of 40-60 MDa size. It is composed of some 500 protein molecules (nucleoporins or nups), arranged in subcomplexes around a central 8-fold rotational axis. Since crystallization of the assembled NPC is impractical for many reasons, we attempt to elucidate first structures of the essential architectural subcomplexes and combine this information in a second step with structural information obtained through single-particle cryo-electron microscopy.