Activity-dependent interdomain dynamics of matrix metalloprotease-1 on fibrin

Result code in 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>

Result on the web

<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>

Result language

angličtina

Original language name

Activity-dependent interdomain dynamics of matrix metalloprotease-1 on fibrin

Original language description

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.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10610 - Biophysics

Project

<a href="/en/project/EF17_050%2F0008496" target="_blank" >EF17_050/0008496: MSCAfellow@MUNI</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Scientific Reports

ISSN

2045-2322

e-ISSN

2045-2322

Volume of the periodical

10

Issue of the periodical within the volume

1

Country of publishing house

DE - GERMANY

Number of pages

14

Pages from-to

1-14

UT code for WoS article

000596325700024

EID of the result in the Scopus database

2-s2.0-85096565328