Related Experiment Video

Updated: Feb 24, 2026

A Fluorogenic Peptide Cleavage Assay to Screen for Proteolytic Activity: Applications for coronavirus spike protein activation
07:53

A Fluorogenic Peptide Cleavage Assay to Screen for Proteolytic Activity: Applications for coronavirus spike protein activation

Published on: January 9, 2019

33.9K

Matriptase shedding is closely coupled with matriptase zymogen activation and requires de novo proteolytic cleavage

Chun-Che Tseng1, Bailing Jia1,2, Robert Barndt1

  • 1Lombardi Comprehensive Cancer Center, Department of Oncology Georgetown University, Washington DC, United States of America.

Plos One
|August 23, 2017
PubMed

Insights

Matriptase shedding, a process prolonging active protease function, is triggered by de novo cleavage at Arg-186. This shedding is coupled to zymogen activation, revealing an autonomous mechanism for active matriptase release.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Matriptase, a type 2 transmembrane serine protease, participates in various pathophysiological processes.
  • Its enzymatic activity is regulated by zymogen activation and protease inhibition.
  • Matriptase shedding can extend the availability of active protease and substrate access.

Purpose of the Study:

  • To investigate the mechanism and regulation of matriptase shedding.
  • To identify the specific cleavage site responsible for matriptase shedding.
  • To elucidate the relationship between matriptase zymogen activation, proteolytic activity, and shedding.

Main Methods:

  • Site-directed mutagenesis of positively charged residues in the SEA-CUB domain region.
  • Kinetic analysis of matriptase zymogen activation and shedding.
  • Functional studies using active site mutants (Ser-805).

Main Results:

  • Matriptase shedding is mediated by de novo proteolytic cleavage between the SEA and CUB domains.
  • Arginine-186 (Arg-186) was identified as the primary cleavage site for matriptase shedding.
  • Matriptase shedding is temporally coupled to and dependent on zymogen activation, occurring approximately one minute after activation.
  • Proteolytic activity of matriptase may contribute to its own shedding.

Conclusions:

  • Matriptase shedding is an autonomous mechanism linked to zymogen activation and proteolytic activity.
  • This shedding allows active matriptase to escape rapid inhibition by HAI-1, releasing it into the extracellular environment.
  • The findings provide new insights into the regulation of matriptase activity and its role in disease.

More Related Videos

Detection of Protease Activity by Fluorescent Peptide Zymography09:56

Detection of Protease Activity by Fluorescent Peptide Zymography

Published on: January 20, 2019

13.6K
Analysis of Transforming Growth Factor ß Family Cleavage Products Secreted Into the Blastocoele of Xenopus laevis Embryos06:57

Analysis of Transforming Growth Factor ß Family Cleavage Products Secreted Into the Blastocoele of Xenopus laevis Embryos

Published on: July 21, 2021

2.8K

Related Concept Videos

Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult...
3.5K
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
13.5K
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
14.3K
Clot Retraction and Fibrinolysis01:16

Clot Retraction and Fibrinolysis

After a fibrin clot is formed, the next step is clot retraction, a vital process facilitated by platelet contractile proteins, such as actin and myosin. These proteins pull the fibrin strands closer together and condense the clot. This action reduces the size of the clot, creating a smaller, denser structure that effectively seals off the damaged vessel. Clot retraction consolidates the clot and helps with wound healing by bringing the edges of the damaged blood vessel closer together.
9.5K
Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70  chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial...
3.8K
Cell Motility through Blebbing01:16

Cell Motility through Blebbing

Blebs are a type of membrane protrusion formed by the internal hydrostatic pressure of the cytoplasm. Blebs are observed in several cell types, including fibroblasts, immune cells, and single-celled organisms like the amoeba. The primary function of blebs is cell locomotion and apoptosis, but they are also found during necrosis and cell division. The life cycle of a bleb comprises an initiation phase followed by the expansion and retraction phases.
Blebbing Through the Matrix
In multicellular...
2.6K