3FP9

Crystal structure of Intern Domain of proteasome-associated ATPase, Mycobacterium tuberculosis

Summary for 3FP9

• Entry DOI: 10.2210/pdb3fp9/pdb
• Descriptor: Proteasome-associated ATPase (2 entities in total)
• Functional Keywords: five strand beta barrel, hexamer, atp-binding, nucleotide-binding, hydrolase, aaa atpase, proteasomal atpase
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 12
• Total formula weight: 200133.73

Authors

Li, H.,Wang, T. (deposition date: 2009-01-04, release date: 2009-10-27, Last modification date: 2024-02-21)

Primary citation

Wang, T.,Li, H.,Lin, G.,Tang, C.,Li, D.,Nathan, C.,Darwin, K.H.,Li, H.
Structural Insights on the Mycobacterium tuberculosis Proteasomal ATPase Mpa.
Structure, 17:1377-1385, 2009

PubMed Abstract: Proteasome-mediated protein turnover in all domains of life is an energy-dependent process that requires ATPase activity. Mycobacterium tuberculosis (Mtb) was recently shown to possess a ubiquitin-like proteasome pathway that plays an essential role in Mtb resistance to killing by products of host macrophages. Here we report our structural and biochemical investigation of Mpa, the presumptive Mtb proteasomal ATPase. We demonstrate that Mpa binds to the Mtb proteasome in the presence of ATPgammaS, providing the physical evidence that Mpa is the proteasomal ATPase. X-ray crystallographic determination of the conserved interdomain showed a five stranded double beta barrel structure containing a Greek key motif. Structure and mutational analysis indicate a major role of the interdomain for Mpa hexamerization. Our mutational and functional studies further suggest that the central channel in the Mpa hexamer is involved in protein substrate translocation and degradation. These studies provide insights into how a bacterial proteasomal ATPase interacts with and facilitates protein degradation by the proteasome.

PubMed: 19836337
DOI: 10.1016/j.str.2009.08.010

Experimental method

X-RAY DIFFRACTION (2 Å)