Mycobacterium tuberculosis proteasomal ATPase Mpa has a β‐grasp domain that hinders docking with the proteasome core protease. Issue 2 (3rd May 2017)

• Record Type: Journal Article
• Authors: Wu, Yujie; Hu, Kuan; Li, Defeng; Bai, Lin; Yang, Shaoqing; Jastrab, Jordan B.; Xiao, Shuhao; Hu, Yonglin; Zhang, Susan; Darwin, K. Heran; Wang, Tao; Li, Huilin
• Is Part Of: Molecular microbiology. Volume 105:Issue 2(2017)
• Page Start: 227
• Page End: 241
• Publication Date: 2017-05-03
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.13695
• Languages: English
• ISSNs: 0950-382X

Abstract

Summary: Mycobacterium tuberculosis ( Mtb ) has a proteasome system that is essential for its ability to cause lethal infections in mice. A key component of the system is the proteasomal adenosine triphosphatase (ATPase) Mpa, which captures, unfolds, and translocates protein substrates into the Mtb proteasome core particle for degradation. Here, we report the crystal structures of near full‐length hexameric Mtb Mpa in apo and ADP‐bound forms. Surprisingly, the structures revealed a ubiquitin‐like β‐grasp domain that precedes the proteasome‐activating carboxyl terminus. This domain, which was only found in bacterial proteasomal ATPases, buries the carboxyl terminus of each protomer in the central channel of the hexamer and hinders the interaction of Mpa with the proteasome core protease. Thus, our work reveals the structure of a bacterial proteasomal ATPase in the hexameric form, and the structure finally explains why Mpa is unable to stimulate robust protein degradation in vitro in the absence of other, yet‐to‐be‐identified co‐factors. Abstract : A portrait of the bacterial proteasomal ATPase hexamer Mpa. The N‐terminal coiled coil domain is responsible for recognizing and recruiting the pupylated protein substrate for degradation by the 20S core protease.