Journal article

Polymerase delta-interacting protein 38 (PDIP38) modulates the stability and activity of the mitochondrial AAA plus protease CLPXP

Philip R Strack, Erica J Brodie, Hanmiao Zhan, Verena J Schuenemann, Liz J Valente, Tamanna Saiyed, Bradley R Lowth, Lauren M Angley, Matthew A Perugini, Kornelius Zeth, Kaye N Truscott, David A Dougan

COMMUNICATIONS BIOLOGY | NATURE RESEARCH | Published : 2020

Abstract

Over a decade ago Polymerase δ interacting protein of 38 kDa (PDIP38) was proposed to play a role in DNA repair. Since this time, both the physiological function and subcellular location of PDIP38 has remained ambiguous and our present understanding of PDIP38 function has been hampered by a lack of detailed biochemical and structural studies. Here we show, that human PDIP38 is directed to the mitochondrion in a membrane potential dependent manner, where it resides in the matrix compartment, together with its partner protein CLPX. Our structural analysis revealed that PDIP38 is composed of two conserved domains separated by an α/β linker region. The N-terminal (YccV-like) domain of PDIP38 for..

View full abstract

University of Melbourne Researchers

Grants

Awarded by Australian Research Council (ARC) Discovery Project


Awarded by ARC Future Fellowship


Awarded by ARC Australian Research Fellowship


Funding Acknowledgements

This work was supported by an Australian Research Council (ARC) Discovery Project (DP0770013) to D.A.D. and K.N.T., and ARC Future Fellowship to K.N.T. (FT0992033) and an ARC Australian Research Fellowship to D.A.D. (DP110103936). P.R.S. and H.Z. were supported by a La Trobe University Postgraduate Award, E.J.B. and B.R.L. were supported by Australian Postgraduate Awards and T.S. was supported by a Cooperative Research Centre postgraduate award. We thank Dr. Clemens Vonrhein from the Buster development group for his help with handling of the crystallographic data and M. Miasari for cloning of PDIP38N and PDIP38C into pGEX-4T.