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Crystal Structure of Mycobacterium Tuberculosis ATP-independent Proteasome Activator TetramerCrystal Structure of Mycobacterium Tuberculosis ATP-independent Proteasome Activator Tetramer
Structural highlights
Publication Abstract from PubMedThe human pathogenMycobacterium 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 theMtbproteasome independently of adenosine triphosphate (ATP). Moreover, PafE contributes to the heat-shock response and virulence ofMtb 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. Structural analysis of the dodecameric proteasome activator PafE in Mycobacterium tuberculosis.,Bai L, Hu K, Wang T, Jastrab JM, Darwin KH, Li H Proc Natl Acad Sci U S A. 2016 Mar 21. pii: 201512094. PMID:27001842[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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