TOWARD THE ATOMIC STRUCTURE OF THE NUCLEAR PORE COMPLEX

Cornell University, Ithaca NY

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Abstract

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.