Sci Adv: The control mechanism of the natural immune system

JANUARY 28, 2021 /--- -- Researchers at Aarhus University have found that a molecule called ITHIH4 inhibits protease activity in the innogeneant immune system through an unknown mechanism.
the protein ITIH4 has been found extensively in the blood, its function is not yet known.
by combining many different techniques, researchers at Aolhus University found that ITIH4 suppresses proteases in the innogenetic immune system through unknown mechanisms.
the findings were published in the journal Science Advance.
(Photo Source: www.pixabay.com) A similar network of proteases called complement systems has been found in our blood and tissues.
the complement system is responsible for eliminating pathogenic organisms, cancer cells and dying cells.
to prevent the complement system from attacking our healthy cells, proteins can instere proteases for a short period of time, putting them under tight control.
these control proteins are called protease inhibitors.
professor Steffen Thiel and student Rasmus Pihl, in the Department of Biomedical Research at Aolhus University, wanted to study which other proteins in our blood interact with so-called MASP proteases in the complement cascade reaction.
found that two MASP proteases formed a strong complex with the ITIH4 protein.
Rasmus and Steffen are now systematically studying how ITIH4 affects MASP-1 and MASP-2.
it turns out that when ITIH4 forms complexes with MASP-1 and MASP-2 enzymes, they can still crack small proteins, while large proteins cannot.
to detail how ITIH4 inhibits MASP proteases, Rasmus Pihl isolated free ITIH4 and ITIH4 in combination with MASP-1 proteases.
using X-ray small-angle scattering and electron microscopes, postdoctoral researcher Rasmus Kjeldsen Jensen and Professor Gregers Rom Andersen, professor of molecular biology and genetics, studied the samples.
that ITIH4 was in contact with MASP-1 protease through the so-called von Willebrand domain, which is very consistent with the findings of the Department of Biomedical Research.
this is a completely new mechanism for inhibiting proteases, which is completely different from the way A2M inhibits proteases.
Now, through a frozen electron microscope, we're trying to learn more about how ITIH4 inhibits MASP-1 and MASP-2 through this new inhibition mechanism," explains Gregers Rom Andersen, a professor at the University of California, California.
we already know that when ITIH4 cleavages, it binds to MASP-1 and another ITIH4 molecule.
" (Bioon.com) Source: Research team discovers new control mechanism in the original source of the immune system: Rasmus Pihl et al, ITIH4 acts as a protease resedor by novel resedory mechanism, Science Advances (2021). DOI: 10.1126/sciadv.aba7381