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

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.

View Accepted Manuscript (DOE)

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

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)

OSTI ID:: 1257964

Alternate ID(s):: OSTI ID: 1347781
OSTI ID: 1354537

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

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

Country of Publication:: United States

Language:: English

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