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

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 + CAPNS1 Δ GR) 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.

Source: Acta Crystallographica Section F - February 4, 2020 Category: Biochemistry Authors: Cresser-Brown, J. Rizkallah, P. Jin, Y. Roth, C. Miller, D.J. Allemann, R.K. Tags: calpain expression Hfq chaperones cysteine protease research communications Source Type: research