| dc.identifier.uri | http://hdl.handle.net/11401/78343 | |
| dc.description.sponsorship | This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree | en_US |
| dc.format | Monograph | |
| dc.format.medium | Electronic Resource | en_US |
| dc.format.mimetype | Application/PDF | en_US |
| dc.language.iso | en_US | |
| dc.type | Dissertation | |
| dcterms.abstract | The proteasome is a large molecular machine for regulated proteolysis. It has been found in all archaea, eukaryotes, and several bacterial species of the order Actinomycetales. Mycobacterium tuberculosis (Mtb), an actinomycete pathogenic to humans, possesses a proteasome system that is essential for its virulence. Two proteasome activators, Mpa and PafE, mediate ATP-dependent and ATP-independent degradation, respectively, in Mtb. The molecular mechanisms of Mtb proteasome activation are still unknown due to the lack of structural information of these two activators. I have utilized several structural biology techniques, complemented with biochemical experiments to gain insights into the structure and function of Mpa and PafE. The crystal structure of PafE revealed a unique dodecameric ring structure. The cryo-EM structure of PafE?155-166 in complex with 20S proteasome showed that the C-terminal GQYL interacts with ?-subunits and facilitates gate opening. Crystal structures of the Mpa hexamer without N-terminal coiled-coils revealed a unique ?-grasp fold near the C-terminus of Mpa, which buries the 20S-binding motif in the central channel and interferes with the interaction between Mpa and 20S proteasome. In sum, my results provide novel structural insights into the mechanisms of ATP-dependent and -independent proteasome activators of Mtb and further the understanding of proteolytic regulation in human pathogen. | |
| dcterms.available | 2018-07-09T13:46:09Z | |
| dcterms.contributor | Garcia-Diaz, Miguel | en_US |
| dcterms.contributor | Li, Huilin. | en_US |
| dcterms.contributor | Seeliger, Markus | en_US |
| dcterms.contributor | Glynn, Steven E. | en_US |
| dcterms.contributor | Darwin, Heran, K. | en_US |
| dcterms.creator | Hu, Kuan | |
| dcterms.dateAccepted | 2018-07-09T13:46:09Z | |
| dcterms.dateSubmitted | 2018-07-09T13:46:09Z | |
| dcterms.description | Department of Biochemistry and Structural Biology. | en_US |
| dcterms.extent | 98 pg. | en_US |
| dcterms.format | Monograph | |
| dcterms.identifier | http://hdl.handle.net/11401/78343 | |
| dcterms.identifier | Hu_grad.sunysb_0771E_13429.pdf | en_US |
| dcterms.issued | 2017-08-01 | |
| dcterms.language | en_US | |
| dcterms.provenance | Submitted by Jason Torre (fjason.torre@stonybrook.edu) on 2018-07-09T13:46:09Z
No. of bitstreams: 1
Hu_grad.sunysb_0771E_13429.pdf: 16630132 bytes, checksum: 0a55be95098bc5a19f765c12f59aa6a5 (MD5) | en |
| dcterms.provenance | Made available in DSpace on 2018-07-09T13:46:09Z (GMT). No. of bitstreams: 1
Hu_grad.sunysb_0771E_13429.pdf: 16630132 bytes, checksum: 0a55be95098bc5a19f765c12f59aa6a5 (MD5)
Previous issue date: 2017-08-01 | en |
| dcterms.subject | Biochemistry | |
| dcterms.title | Structural Insights into Proteasome Activators in Mycobacterium tuberculosis | |
| dcterms.type | Dissertation | |
