English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

The bait region of the general protease inhibitor alpha 2-macroglobulin (alpha 2M) was mutated by introducing a recognition sequence of furin. This did not interfere with folding, S-ester formation or tetramerization of the mutant recombinant alpha 2M (r alpha 2M). Mutant r alpha 2M inhibited furin in vitro, by a similar mechanism to that used by plasma alpha 2M to inhibit high-molecular-mass proteases. The mutant alpha 2M was intracellularly active in COS-1 cells in inhibiting the endogenous processing of the soluble substrates for furin (von Willebrand factor, transforming growth factor beta1 and a soluble form of the envelope glycoprotein gp160 from HIV-1) but not the membrane-bound form of gp160. The intracellular activity of mutant alpha 2M strongly indicated that alpha 2M attains its native conformation, and thus that the unusual internal S-ester is formed, before alpha 2M passes through the cleavage compartment(s). Our results show for the first time that modulation of the bait region of alpha 2M allows the creation of an inhibitor against membrane-bound proteases. It can be expected that the use of alpha 2M-bait mutants will become important as a technique for the study of various proteolytic processes and for the identification of the proteases involved.

biochemical journal

Inhibition of intracellular proteolytic processing of soluble proproteins by an engineered <i>α</i>2-macroglobulin containing a furin recognition sequence in the bait region

Inhibition of intracellular proteolytic processing of soluble proproteins by an engineered α2-macroglobulin containing a furin recognition sequence in the bait region