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• W2170555731 endingPage "4740" @default.
• W2170555731 startingPage "4728" @default.
• W2170555731 abstract "The matrix metalloproteinases (MMPs) are a family of secreted soluble or membrane-anchored multimodular peptidases regularly found in several paralogous copies in animals and plants, where they have multiple functions. The minimal consensus domain architecture comprises a signal peptide, a 60–90-residue globular prodomain with a conserved sequence motif including a cysteine engaged in “cysteine-switch” or “Velcro” mediated latency, and a catalytic domain. Karilysin, from the human periodontopathogen Tannerella forsythia, is the only bacterial MMP to have been characterized biochemically to date. It shares with eukaryotic forms the catalytic domain but none of the flanking domains. Instead of the consensus MMP prodomain, it features a 14-residue propeptide, the shortest reported for a metallopeptidase, which lacks cysteines. Here we determined the structure of a prokarilysin fragment encompassing the propeptide and the catalytic domain, and found that the former runs across the cleft in the opposite direction to a bound substrate and inhibits the latter through an “aspartate-switch” mechanism. This finding is reminiscent of latency maintenance in the otherwise unrelated astacin and fragilysin metallopeptidase families. In addition, in vivo and biochemical assays showed that the propeptide contributes to protein folding and stability. Our analysis of prokarilysin reveals a novel mechanism of latency and activation in MMPs. Finally, our findings support the view that the karilysin catalytic domain was co-opted by competent bacteria through horizontal gene transfer from a eukaryotic source, and later evolved in a specific bacterial environment. The matrix metalloproteinases (MMPs) are a family of secreted soluble or membrane-anchored multimodular peptidases regularly found in several paralogous copies in animals and plants, where they have multiple functions. The minimal consensus domain architecture comprises a signal peptide, a 60–90-residue globular prodomain with a conserved sequence motif including a cysteine engaged in “cysteine-switch” or “Velcro” mediated latency, and a catalytic domain. Karilysin, from the human periodontopathogen Tannerella forsythia, is the only bacterial MMP to have been characterized biochemically to date. It shares with eukaryotic forms the catalytic domain but none of the flanking domains. Instead of the consensus MMP prodomain, it features a 14-residue propeptide, the shortest reported for a metallopeptidase, which lacks cysteines. Here we determined the structure of a prokarilysin fragment encompassing the propeptide and the catalytic domain, and found that the former runs across the cleft in the opposite direction to a bound substrate and inhibits the latter through an “aspartate-switch” mechanism. This finding is reminiscent of latency maintenance in the otherwise unrelated astacin and fragilysin metallopeptidase families. In addition, in vivo and biochemical assays showed that the propeptide contributes to protein folding and stability. Our analysis of prokarilysin reveals a novel mechanism of latency and activation in MMPs. Finally, our findings support the view that the karilysin catalytic domain was co-opted by competent bacteria through horizontal gene transfer from a eukaryotic source, and later evolved in a specific bacterial environment." @default.
• W2170555731 created "2016-06-24" @default.
• W2170555731 creator A5023079125 @default.
• W2170555731 creator A5034381369 @default.
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• W2170555731 creator A5070856702 @default.
• W2170555731 creator A5079332993 @default.
• W2170555731 creator A5087231208 @default.
• W2170555731 creator A5088089769 @default.
• W2170555731 date "2015-02-01" @default.
• W2170555731 modified "2023-10-14" @default.
• W2170555731 title "A Novel Mechanism of Latency in Matrix Metalloproteinases" @default.
• W2170555731 cites W1505402212 @default.
• W2170555731 cites W1506994069 @default.
• W2170555731 cites W1568920274 @default.
• W2170555731 cites W1607581180 @default.
• W2170555731 cites W170140184 @default.
• W2170555731 cites W1835135188 @default.
• W2170555731 cites W1935587632 @default.
• W2170555731 cites W1964428785 @default.
• W2170555731 cites W1966897949 @default.
• W2170555731 cites W1968539554 @default.
• W2170555731 cites W1969885133 @default.
• W2170555731 cites W1976259855 @default.
• W2170555731 cites W1976996080 @default.
• W2170555731 cites W1978318542 @default.
• W2170555731 cites W1979576286 @default.
• W2170555731 cites W1980742802 @default.
• W2170555731 cites W1984319347 @default.
• W2170555731 cites W1985078397 @default.
• W2170555731 cites W1985469117 @default.
• W2170555731 cites W1991063206 @default.
• W2170555731 cites W1995017064 @default.
• W2170555731 cites W1995518402 @default.
• W2170555731 cites W1996072545 @default.
• W2170555731 cites W1996962373 @default.
• W2170555731 cites W2001326121 @default.
• W2170555731 cites W2012215782 @default.
• W2170555731 cites W2014932306 @default.
• W2170555731 cites W2017306282 @default.
• W2170555731 cites W2017537859 @default.
• W2170555731 cites W2018407041 @default.
• W2170555731 cites W2019838731 @default.
• W2170555731 cites W2021116136 @default.
• W2170555731 cites W2022284401 @default.
• W2170555731 cites W2026863841 @default.
• W2170555731 cites W2029196705 @default.
• W2170555731 cites W2032452880 @default.
• W2170555731 cites W2037131689 @default.
• W2170555731 cites W2040764826 @default.
• W2170555731 cites W2044292829 @default.
• W2170555731 cites W2044503036 @default.
• W2170555731 cites W2048356493 @default.
• W2170555731 cites W2050023553 @default.
• W2170555731 cites W2052605451 @default.
• W2170555731 cites W2055580270 @default.
• W2170555731 cites W2055999347 @default.
• W2170555731 cites W2056531111 @default.
• W2170555731 cites W2057200339 @default.
• W2170555731 cites W2058197352 @default.
• W2170555731 cites W2059222613 @default.
• W2170555731 cites W2059919196 @default.
• W2170555731 cites W2061220971 @default.
• W2170555731 cites W2062254347 @default.
• W2170555731 cites W2069456989 @default.
• W2170555731 cites W2072176101 @default.
• W2170555731 cites W2073607085 @default.
• W2170555731 cites W2073920564 @default.
• W2170555731 cites W2076798977 @default.
• W2170555731 cites W2078269233 @default.
• W2170555731 cites W2083699890 @default.
• W2170555731 cites W2086441450 @default.
• W2170555731 cites W2086447944 @default.
• W2170555731 cites W2086825339 @default.
• W2170555731 cites W2089719502 @default.
• W2170555731 cites W2094001260 @default.
• W2170555731 cites W2108921801 @default.
• W2170555731 cites W2108959691 @default.
• W2170555731 cites W2111988212 @default.
• W2170555731 cites W2120717049 @default.
• W2170555731 cites W2121040393 @default.
• W2170555731 cites W2122266747 @default.
• W2170555731 cites W2123073660 @default.
• W2170555731 cites W2124026197 @default.
• W2170555731 cites W2129531904 @default.
• W2170555731 cites W2132629607 @default.
• W2170555731 cites W2133197433 @default.
• W2170555731 cites W2136244824 @default.
• W2170555731 cites W2136255360 @default.
• W2170555731 cites W2136567909 @default.
• W2170555731 cites W2136600834 @default.
• W2170555731 cites W2139074914 @default.
• W2170555731 cites W2141186509 @default.
• W2170555731 cites W2143550120 @default.
• W2170555731 cites W2144998676 @default.
• W2170555731 cites W2145696686 @default.
• W2170555731 cites W2147874841 @default.
• W2170555731 cites W2154197653 @default.

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