5IEU

Crystal Structure of Mycobacterium Tuberculosis ATP-independent Proteasome Activator Tetramer

Summary for 5IEU

• Entry DOI: 10.2210/pdb5ieu/pdb
• Related: 5IET
• Descriptor: Bacterial proteasome activator (2 entities in total)
• Functional Keywords: activator, gene regulation
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 2
• Total formula weight: 27575.45

Authors

Bai, L.,Hu, K.,Wang, T.,Jastrab, J.B.,Darwin, K.H.,Li, H. (deposition date: 2016-02-25, release date: 2016-03-30, Last modification date: 2024-03-06)

Primary citation

Bai, L.,Hu, K.,Wang, T.,Jastrab, J.B.,Darwin, K.H.,Li, H.
Structural analysis of the dodecameric proteasome activator PafE in Mycobacterium tuberculosis.
Proc.Natl.Acad.Sci.USA, 113:E1983-E1992, 2016

PubMed Abstract: The human pathogen Mycobacterium tuberculosis (Mtb) requires a proteasome system to cause lethal infections in mice. We recently found that proteasome accessory factor E (PafE, Rv3780) activates proteolysis by the Mtb proteasome independently of adenosine triphosphate (ATP). Moreover, PafE contributes to the heat-shock response and virulence of Mtb Here, we show that PafE subunits formed four-helix bundles similar to those of the eukaryotic ATP-independent proteasome activator subunits of PA26 and PA28. However, unlike any other known proteasome activator, PafE formed dodecamers with 12-fold symmetry, which required a glycine-XXX-glycine-XXX-glycine motif that is not found in previously described activators. Intriguingly, the truncation of the PafE carboxyl-terminus resulted in the robust binding of PafE rings to native proteasome core particles and substantially increased proteasomal activity, suggesting that the extended carboxyl-terminus of this cofactor confers suboptimal binding to the proteasome core particle. Collectively, our data show that proteasomal activation is not limited to hexameric ATPases in bacteria.

PubMed: 27001842
DOI: 10.1073/pnas.1512094113

Experimental method

X-RAY DIFFRACTION (2.8 Å)