An unexpected co-crystal structure of the calpain PEF(S) domain with Hfq reveals a potential chaperone function of Hfq.

Joel Cresser-Brown, Pierre Rizkallah, Yi Jin, Christian Roth, David J Miller, Rudolf K Allemann

Acta crystallographica. Section F, Structural biology communications 2020 Feb 01

filter terms:

Calpain is a Ca2+-activated, heterodimeric cysteine protease consisting of a large catalytic subunit and a small regulatory subunit. Dysregulation of this enzyme is involved in a range of pathological conditions such as cancer, Alzheimer's disease and rheumatoid arthritis, and thus calpain I is a drug target with potential therapeutic applications. Difficulty in the production of this enzyme has hindered structural and functional investigations in the past, although heterodimeric calpain I can be generated by Escherichia coli expression in low yield. Here, an unexpected structure discovered during crystallization trials of heterodimeric calpain I (CAPN1C115S + CAPNS1ΔGR) is reported. A novel co-crystal structure of the PEF(S) domain from the dissociated regulatory small subunit of calpain I and the RNA-binding chaperone Hfq, which was likely to be overproduced as a stress response to the recombinant expression conditions, was obtained, providing unexpected insight in the chaperone function of Hfq.

Citation

Joel Cresser-Brown, Pierre Rizkallah, Yi Jin, Christian Roth, David J Miller, Rudolf K Allemann. An unexpected co-crystal structure of the calpain PEF(S) domain with Hfq reveals a potential chaperone function of Hfq. Acta crystallographica. Section F, Structural biology communications. 2020 Feb 01;76(Pt 2):81-85