Journal Article

FZJ-2021-03503

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The Peptide Ligase Activity of Human Legumain Depends on Fold Stabilization and Balanced Substrate Affinities

Dall, E. (Corresponding author) ; Stanojlovic, V. ; Demir, F. ; Briza, P. ; Dahms, S. O. ; Huesgen, P. F.FZJ* ; Cabrele, C. ; Brandstetter, H. (Corresponding author)

2021
ACS Washington, DC

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Please use a persistent id in citations: http://hdl.handle.net/2128/28721  doi:10.1021/acscatal.1c02057

Abstract: Protein modification by enzymatic breaking and forming of peptide bonds significantly expands the repertoire of genetically encoded protein sequences. The dual protease-ligase legumain exerts the two opposing activities within a single protein scaffold. Primarily localized to the endolysosomal system, legumain represents a key enzyme in the generation of antigenic peptides for subsequent presentation on the MHCII complex. Here we show that human legumain catalyzes the ligation and cyclization of linear peptides at near-neutral pH conditions, where legumain is intrinsically unstable. Conformational stabilization significantly enhanced legumain’s ligase activity, which further benefited from engineering the prime substrate recognition sites for improved affinity. Additionally, we provide evidence that specific legumain activation states allow for differential regulation of its activities. Together these results set the basis for engineering legumain proteases and ligases with applications in biotechnology and drug development.

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Contributing Institute(s):

1. Analytik (ZEA-3)

Research Program(s):

1. 2171 - Biological and environmental resources for sustainable use (POF4-217) (POF4-217)
2. ProPlantStress - Proteolytic processing in plant stress signal transduction and responses to abiotic stress and pathogen attack (639905) (639905)

Appears in the scientific report 2021

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Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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