An unexpected co‐crystal structure of the calpain PEF(S) domain with Hfq reveals a potential chaperone function of Hfq. Issue 2 (10th February 2020)

• Record Type: Journal Article
• Authors: Cresser-Brown, Joel; Rizkallah, Pierre; Jin, Yi; Roth, Christian; Miller, David J.; Allemann, Rudolf K.
• Is Part Of: Acta crystallographica. Volume 76:Issue 2(2020:Feb.)
• Page Start: 81
• Page End: 85
• Publication Date: 2020-02-10
• Subjects: calpain expression -- Hfq -- chaperones -- cysteine protease; Crystallography -- Periodicals; Crystals -- Periodicals; 548
• DOI: 10.1107/S2053230X20001181
• Languages: English
• ISSNs: 2053-230X

Abstract

Abstract : A co‐crystal structure of the calpain PEF(S) domain bound to the Escherichia coli chaperone Hfq provides insight into the pitfalls of expression of the full‐length heterodimeric calpain I complex. Abstract : Calpain is a Ca 2+ ‐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.