Molecular and structural insights into an asymmetric proteolytic complex (ClpP1P2) from Mycobacterium smegmatis

Nagpal, Jyotsna; Paxman, Jason; Zammit, Jessica; Alhuwaider, Adnan; Truscott, Kaye; Heras, Begona; Dougan, David

doi:10.1038/s41598-019-53736-8

Molecular and structural insights into an asymmetric proteolytic complex (ClpP1P2) from Mycobacterium smegmatis

journal contribution

posted on 2025-01-14, 02:42 authored by Jyotsna Nagpal, Jason PaxmanJason Paxman, Jessica ZammitJessica Zammit, Adnan Alhuwaider, Kaye TruscottKaye Truscott, Begona HerasBegona Heras, David DouganDavid Dougan

The ClpP protease is found in all kingdoms of life, from bacteria to humans. In general, this protease forms a homo-oligomeric complex composed of 14 identical subunits, which associates with its cognate ATPase in a symmetrical manner. Here we show that, in contrast to this general architecture, the Clp protease from Mycobacterium smegmatis (Msm) forms an asymmetric hetero-oligomeric complex ClpP1P2, which only associates with its cognate ATPase through the ClpP2 ring. Our structural and functional characterisation of this complex demonstrates that asymmetric docking of the ATPase component is controlled by both the composition of the ClpP1 hydrophobic pocket (Hp) and the presence of a unique C-terminal extension in ClpP1 that guards this Hp. Our structural analysis of MsmClpP1 also revealed openings in the side-walls of the inactive tetradecamer, which may represent sites for product egress.

Funding

D.A.D. was supported by an Australian Research Council (ARC) Australian Research Fellowship (DP110103936) and B.H. was supported by an ARC Future Fellowship (FT130100580). The work was supported by a Victoria India Doctoral Scholarship (to J.N.), La Trobe University Postgraduate Research Scholarships (to J.E.Z. and A.A.T.) and La Trobe University Full Fee Research Scholarships (to J.N and A.A.T.).

History

Publication Date

2019-12-02

Journal

Scientific Reports

Volume

9

Article Number

18019

Pagination

12p.

Publisher

Springer Nature

ISSN

2045-2322

Rights Statement

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