Activity-dependent interdomain dynamics of matrix metalloprotease-1 on fibrin
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F20%3A00118002" target="_blank" >RIV/00216224:14310/20:00118002 - isvavai.cz</a>
Výsledek na webu
<a href="https://www.nature.com/articles/s41598-020-77699-3" target="_blank" >https://www.nature.com/articles/s41598-020-77699-3</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41598-020-77699-3" target="_blank" >10.1038/s41598-020-77699-3</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Activity-dependent interdomain dynamics of matrix metalloprotease-1 on fibrin
Popis výsledku v původním jazyce
The roles of protein conformational dynamics and allostery in function are well-known. However, the roles that interdomain dynamics have in function are not entirely understood. We used matrix metalloprotease-1 (MMP1) as a model system to study the relationship between interdomain dynamics and activity because MMP1 has diverse substrates. Here we focus on fibrin, the primary component of a blood clot. Water-soluble fibrinogen, following cleavage by thrombin, self-polymerize to form water-insoluble fibrin. We studied the interdomain dynamics of MMP1 on fibrin without crosslinks using single-molecule Forster Resonance Energy Transfer (smFRET). We observed that the distance between the catalytic and hemopexin domains of MMP1 increases or decreases as the MMP1 activity increases or decreases, respectively. We modulated the activity using (1) an active site mutant (E219Q) of MMP1, (2) MMP9, another member of the MMP family that increases the activity of MMP1, and (3) tetracycline, an inhibitor of MMP1. We fitted the histograms of smFRET values to a sum of two Gaussians and the autocorrelations to an exponential and power law. We modeled the dynamics as a two-state Poisson process and calculated the kinetic rates from the histograms and autocorrelations. Activity-dependent interdomain dynamics may enable allosteric control of the MMP1 function.
Název v anglickém jazyce
Activity-dependent interdomain dynamics of matrix metalloprotease-1 on fibrin
Popis výsledku anglicky
The roles of protein conformational dynamics and allostery in function are well-known. However, the roles that interdomain dynamics have in function are not entirely understood. We used matrix metalloprotease-1 (MMP1) as a model system to study the relationship between interdomain dynamics and activity because MMP1 has diverse substrates. Here we focus on fibrin, the primary component of a blood clot. Water-soluble fibrinogen, following cleavage by thrombin, self-polymerize to form water-insoluble fibrin. We studied the interdomain dynamics of MMP1 on fibrin without crosslinks using single-molecule Forster Resonance Energy Transfer (smFRET). We observed that the distance between the catalytic and hemopexin domains of MMP1 increases or decreases as the MMP1 activity increases or decreases, respectively. We modulated the activity using (1) an active site mutant (E219Q) of MMP1, (2) MMP9, another member of the MMP family that increases the activity of MMP1, and (3) tetracycline, an inhibitor of MMP1. We fitted the histograms of smFRET values to a sum of two Gaussians and the autocorrelations to an exponential and power law. We modeled the dynamics as a two-state Poisson process and calculated the kinetic rates from the histograms and autocorrelations. Activity-dependent interdomain dynamics may enable allosteric control of the MMP1 function.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
10610 - Biophysics
Návaznosti výsledku
Projekt
<a href="/cs/project/EF17_050%2F0008496" target="_blank" >EF17_050/0008496: MSCAfellow@MUNI</a><br>
Návaznosti
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Ostatní
Rok uplatnění
2020
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Scientific Reports
ISSN
2045-2322
e-ISSN
2045-2322
Svazek periodika
10
Číslo periodika v rámci svazku
1
Stát vydavatele periodika
DE - Spolková republika Německo
Počet stran výsledku
14
Strana od-do
1-14
Kód UT WoS článku
000596325700024
EID výsledku v databázi Scopus
2-s2.0-85096565328