Cucurbit[8]uril reactivation of an inactivated caspase-8 mutant reveals differentiated enzymatic substrate processing

Dung T. Dang, Arthur H.A.M. van Onzen, Yvonne L. Dorland, Luc Brunsveld

Onderzoeksoutput: Bijdrage aan tijdschriftTijdschriftartikelAcademicpeer review

4 Citaten (Scopus)
46 Downloads (Pure)

Samenvatting

Caspase-8 constructs featuring an N-terminal FGG sequence allow for selective twofold recognition by cucurbit[8]uril, which leads to an increase of the enzymatic activity in a cucurbit[8]uril dose-dependent manner. This supramolecular switching has enabled for the first time the study of the same caspase-8 in its two extreme states; as full monomer and as cucurbit[8]uril induced dimer. A mutated, fully monomeric caspase-8 (D384A), which is enzymatically inactive towards its natural substrate caspase-3, could be fully reactivated upon addition of cucurbit[8]uril. In its monomeric state caspase-8 (D384A) still processes a small synthetic substrate, but not the natural caspase-3 substrate, highlighting the close interplay between protein dimerization and active site rearrangement for substrate selectivity. The ability to switch the caspase-8 activity by a supramolecular system thus provides a flexible approach to studying the activity of a protein at different oligomerization states.

Originele taal-2Engels
Pagina's (van-tot)2490-2494
Aantal pagina's5
TijdschriftChemBioChem
Volume19
Nummer van het tijdschrift23
DOI's
StatusGepubliceerd - 4 dec 2018

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