MMP-14 degrades tropoelastin and elastin

Natalia Miękus , Chiara Luise , Wolfgang Sippl , Tomasz Bączek , Christian E. H. Schmelzer , Andrea Heinz

Abstract

Matrix metalloproteinases are a class of enzymes, which degrade extracellular matrix components such as collagens, elastin, laminin or fibronectin. So far, four matrix metalloproteinases have been shown to degrade elastin and its precursor tropoelastin, namely matrix metalloproteinase-2, -7, -9 and -12. This study focuses on investigating the elastinolytic capability of membrane-type 1 matrix metalloproteinase, also known as matrix metalloproteinase-14. We digested recombinant human tropoelastin and human skin elastin with matrix metalloproteinase-14 and analyzed the peptide mixtures using complementary mass spectrometric techniques and bioinformatics tools. The results and additional molecular docking studies show that matrix metalloproteinase-14 cleaves tropoelastin as well as elastin. While tropoelastin was well degraded, fewer cleavages occurred in the highly cross-linked mature elastin. The study also provides insights into the cleavage preferences of the enzyme. Similar to cleavage preferences of matrix metalloproteinases-2, -7, -9 and -12, matrix metalloproteinase-14 prefers small and medium-sized hydrophobic residues including Gly, Ala, Leu and Val at cleavage site P1’. Pro, Gly and Ala were preferably found at P1-P4 and P2′-P4′ in both tropoelastin and elastin. Cleavage of mature skin elastin by matrix metalloproteinase-14 released a variety of bioactive elastin peptides, which indicates that the enzyme may play a role in the development and progression of cardiovascular diseases that go along with elastin breakdown.
Author Natalia Miękus (FB / DAHP)
Natalia Miękus,,
- Department of Animal and Human Physiology
, Chiara Luise
Chiara Luise,,
-
, Wolfgang Sippl
Wolfgang Sippl,,
-
, Tomasz Bączek
Tomasz Bączek,,
-
, Christian E. H. Schmelzer
Christian E. H. Schmelzer,,
-
, Andrea Heinz
Andrea Heinz,,
-
Journal seriesBiochimie, ISSN 0300-9084, (A 25 pkt)
Issue year2019
Vol165
Pages32-39
Publication size in sheets0.5
Keywords in EnglishMass spectrometry, metalloproteinases, MT-MMPs, proteomics, extracellular matrix, elastases
ASJC Classification2700 General Medicine; 1303 Biochemistry
DOIDOI:10.1016/j.biochi.2019.07.001
URL https://doi.org/10.1016/j.biochi.2019.07.001
Languageen angielski
Score (nominal)25
ScoreMinisterial score = 25.0, 08-08-2019, ArticleFromJournal
Publication indicators Scopus SNIP (Source Normalised Impact per Paper): 2016 = 0.975; WoS Impact Factor: 2017 = 3.188 (2) - 2017=3.058 (5)
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