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

J 2020

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

KUMAR, Lokender; Joan PLANAS IGLESIAS; Chase HARMS; Sumaer KAMBOJ; Derek WRIGHT et al.

Základní údaje

Originální název

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

Autoři

KUMAR, Lokender; Joan PLANAS IGLESIAS; Chase HARMS; Sumaer KAMBOJ; Derek WRIGHT; Judith KLEIN-SEETHARAMAN a K.Susanta SARKAR

Vydání

Scientific Reports, Berlin, Nature Research, 2020, 2045-2322

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10610 Biophysics

Stát vydavatele

Německo

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.380

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/20:00118002

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

Biophysics; Molecular biophysics; Molecular conformation

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 15. 2. 2021 10:38, Mgr. Marie Novosadová Šípková, DiS.

Anotace

V originále

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.

Návaznosti

EF17_050/0008496, projekt VaV

Název: MSCAfellow@MUNI

Citovat

KUMAR, Lokender; Joan PLANAS IGLESIAS; Chase HARMS; Sumaer KAMBOJ; Derek WRIGHT; Judith KLEIN-SEETHARAMAN a K.Susanta SARKAR. Activity-dependent interdomain dynamics of matrix metalloprotease-1 on fibrin. Scientific Reports. Berlin: Nature Research, 2020, roč. 10, č. 1, s. 1-14. ISSN 2045-2322. Dostupné z: https://doi.org/10.1038/s41598-020-77699-3.

@article{1733398,
   author = {Kumar, Lokender and Planas Iglesias, Joan and Harms, Chase and Kamboj, Sumaer and Wright, Derek and KleinandSeetharaman, Judith and Sarkar, K.Susanta},
   article_location = {Berlin},
   article_number = {1},
   doi = {https://doi.org/10.1038/s41598-020-77699-3},
   keywords = {Biophysics; Molecular biophysics; Molecular conformation},
   language = {eng},
   issn = {2045-2322},
   journal = {Scientific Reports},
   title = {Activity-dependent interdomain dynamics of matrix metalloprotease-1 on fibrin},
   url = {https://www.nature.com/articles/s41598-020-77699-3},
   volume = {10},
   year = {2020}
}

TY  - JOUR
ID  - 1733398
AU  - Kumar, Lokender - Planas Iglesias, Joan - Harms, Chase - Kamboj, Sumaer - Wright, Derek - Klein-Seetharaman, Judith - Sarkar, K.Susanta
PY  - 2020
TI  - Activity-dependent interdomain dynamics of matrix metalloprotease-1 on fibrin
JF  - Scientific Reports
VL  - 10
IS  - 1
SP  - 1-14
EP  - 1-14
PB  - Nature Research
SN  - 20452322
KW  - Biophysics
KW  - Molecular biophysics
KW  - Molecular conformation
UR  - https://www.nature.com/articles/s41598-020-77699-3
L2  - https://www.nature.com/articles/s41598-020-77699-3
N2  - 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.
ER  -

KUMAR, Lokender; Joan PLANAS IGLESIAS; Chase HARMS; Sumaer KAMBOJ; Derek WRIGHT; Judith KLEIN-SEETHARAMAN a K.Susanta SARKAR. Activity-dependent interdomain dynamics of matrix metalloprotease-1 on fibrin. \textit{Scientific Reports}. Berlin: Nature Research, 2020, roč.~10, č.~1, s.~1-14. ISSN~2045-2322. Dostupné z: https://doi.org/10.1038/s41598-020-77699-3.

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