CRYSTALLOGRAPHIC STUDIES ON NUCLEAR PORE COMPLEX PROTEINS

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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.