Structural analysis of the dodecameric proteasome activator PafE in Mycobacterium tuberculosis

Bai, Lin; Hu, Kuan; Wang, Tong; Jastrab, Jordan B.; Darwin, K. Heran; Li, Huilin

doi:10.1073/pnas.1512094113

Title: Structural analysis of the dodecameric proteasome activator PafE in Mycobacterium tuberculosis

Journal Article · Mon Mar 21 00:00:00 EDT 2016 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.1512094113· OSTI ID:1257964

Bai, Lin ^[1]; Hu, Kuan ^[2]; Wang, Tong ^[1]; Jastrab, Jordan B. ^[3]; Darwin, K. Heran ^[3]; Li, Huilin ^[2]

Brookhaven National Lab. (BNL), Upton, NY (United States)
Brookhaven National Lab. (BNL), Upton, NY (United States); Stony Brook Univ., Stony Brook, NY (United States)
New York Univ. School of Medicine, New York, NY (United States)

Here, 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.

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Research Organization:: Brookhaven National Laboratory (BNL), Upton, NY (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: SC00112704

OSTI ID:: 1257964

Report Number(s):: BNL-112309-2016-JA

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, Issue 14; ISSN 0027-8424

Country of Publication:: United States

Language:: English

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Cited by: 19 works

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