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Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

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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...
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Matrix Proteoglycans and Glycoproteins01:21

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Proteoglycans are extensively glycosylated proteins, commonly found in the extracellular matrix, interwoven with collagen fibers. Hyaline cartilage, the most common type of cartilage in the body, consists of short and dispersed collagen fibers associated with large amounts of proteoglycans. These proteoglycans have long negative charges that attract cations, which in turn attract water molecules. This influx of ions and water molecules swells up the proteoglycan like a water-soaked gel that can...
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Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
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Assembly of Signaling Complexes01:30

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Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
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Fibril-associated Collagen01:11

Fibril-associated Collagen

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Fibril-associated collagens are a type of collagens present in the extracellular matrix with interrupted triple helices or FACIT (Fibril-associated collagens interrupted triple-helices). FACIT help connect and attach the collagen fibrils with each other as well as with other proteins of the extracellular matrix.
For example, the type II collagen fibrils in cartilage have covalently bound type IX fibril-associated collagens at regular intervals. Other types of fibril-associated collagens are...
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Translocation of Proteins into the Mitochondria01:19

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Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
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Related Experiment Video

Updated: Dec 18, 2025

X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep1050
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Molecular Interactions Stabilizing the Promatrix Metalloprotease-9·Serglycin Heteromer.

Rangita Dawadi1, Nabin Malla1, Beate Hegge1

  • 1Department of Medical Biology, Faculty of Health Sciences, UiT-The Arctic University of Norway, 9037 Tromsø, Norway.

International Journal of Molecular Sciences
|June 18, 2020
PubMed
Summary

This study reveals that the chondroitin sulfate proteoglycan (CSPG) core protein and serglycin (SG) bind pro matrix metalloproteinase-9 (proMMP-9) via extensive interactions. These interactions involve the FnII module and HPX domain, explaining the complex

Keywords:
dockingin vitro reconstitutionmolecular dynamics simulationmolecular modellingpeptide arraysproMMP-9proMMP-9 complexesproMMP-9 deletion variantsserglycin

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • Previous studies identified an SDS-stable and reduction-sensitive complex between pro matrix metalloproteinase-9 (proMMP-9) and chondroitin sulfate proteoglycan (CSPG) core protein in THP-1 cells.
  • This complex could be reconstituted in vitro using purified serglycin (SG) and proMMP-9, lacking inter-disulfide bridges.
  • The interaction was hypothesized to involve the FnII module and HPX domain of proMMP-9.

Purpose of the Study:

  • To precisely identify the interacting regions between proMMP-9 and CSPG/SG that form the complex.
  • To elucidate the specific types of molecular interactions mediating this binding.
  • To understand the structural basis for the observed SDS-stable and reduction-sensitive complex.

Main Methods:

  • Expression and purification of full-length and deletion variants of proMMP-9.
  • Purification of chondroitin sulfate proteoglycan (CSPG) and serglycin (SG).
  • In vitro reconstitution assays, peptide arrays, protein modeling, molecular docking, and molecular dynamics (MD) simulations.

Main Results:

  • ProMMP-9 variants lacking both the FnII module and HPX domain failed to form the complex.
  • Variants possessing either the FnII module or the HPX domain, as well as SG core protein alone, successfully formed the proMMP-9∙CSPG/SG complex.
  • Interactions involved large surface areas and included dynamic ionic, hydrophobic, and hydrogen bond interactions, rather than short linear motifs.

Conclusions:

  • The FnII module and HPX domain of proMMP-9 are crucial for binding to CSPG/SG.
  • The proMMP-9∙CSPG/SG complex is stabilized by extensive, multi-modal interactions (ionic, hydrophobic, hydrogen bonds) across large molecular surfaces.
  • The strong, SDS-stable, and reduction-sensitive nature of the complex is attributed to these broad interactions, not single binding sites.