Integrative Structure Determination Using Proteomics Data: Application to the Nuclear Pore Complex
- Author(s): Phillips, Jeremy
- Advisor(s): Sali, Andrej
- et al.
Proteomics techniques have been used to generate comprehensive lists of protein interactions in a number of species. However, relatively little is known about how these interactions result in functional multiprotein complexes. This dissertation describes a computational procedure that bridges this gap by combining low-resolution data from affinity purification experiments with data from a heterogenous set of standard structural biology techniques, including electron microscopy (EM) and X-ray crystallography. One such assembly is the Nuclear Pore Complex (NPC), which serves as the sole mediator of nucleocytoplasmic exchange in eukaryotic cells. We used our method to determine the structure of the ~600 kDa heptameric Nup84 complex, an essential component of the NPC. This work demonstrates that integrative approaches based on low-resolution data can generate functionally informative structures at intermediate resolution.