Allosteric Communications between Domains Modulate the Activity
of Matrix Metalloprotease-1

J 2020

Allosteric Communications between Domains Modulate the Activity of Matrix Metalloprotease-1

KUMAR, Lokender, Anthony NASH, Chase HARMS, Joan PLANAS IGLESIAS, Derek WRIGHT et. al.

Základní údaje

Originální název

Allosteric Communications between Domains Modulate the Activity of Matrix Metalloprotease-1

Autoři

KUMAR, Lokender, Anthony NASH, Chase HARMS, Joan PLANAS IGLESIAS (724 Španělsko, garant, domácí), Derek WRIGHT, Judith KLEIN-SEETHARAMAN a Susanta K SARKAR

Vydání

Biophysical Journal, Bethesda, USA, Biophysical Society, 2020, 0006-3495

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10610 Biophysics

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.033

Kód RIV

RIV/00216224:14310/20:00116405

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.1016/j.bpj.2020.06.010

UT WoS

000552027100014

Klíčová slova anglicky

triple-helical collagen; power-law correlations; anisotropic network model; focal cerebral ischemia

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 14. 9. 2020 10:35, Mgr. Marie Šípková, DiS.

Anotace

V originále

An understanding of the structure-dynamics relationship is essential for understanding how a protein works. Prior research has shown that the activity of a protein correlates with intradomain dynamics occurring at picosecond to millisecond timescales. However, the correlation between interdomain dynamics and the function of a protein is poorly understood. Here, we show that communications between the catalytic and hemopexin domains of matrix metalloprotease-1 (MMP1) on type 1 collagen fibrils correlate with its activity. Using single-molecule Forster resonance energy transfer, we identified functionally relevant open conformations in which the two MMP1 domains are well separated, which were significantly absent for catalytically inactive point mutant (E219Q) of MMP1 and could be modulated by an inhibitor or an enhancer of activity. The observed relevance of open conformations resolves the debate about the roles of open and closed MMP1 structures in function. We fitted the histograms of single-molecule Forster resonance energy transfer values to a sum of two Gaussians and the autocorrelations to an exponential and power law. We used a two-state Poisson process to describe the dynamics and calculate the kinetic rates from the fit parameters. All-atom and coarse-grained simulations reproduced some of the experimental features and revealed substrate-dependent MMP1 dynamics. Our results suggest that an interdomain separation facilitates opening up the catalytic pocket so that the collagen chains come closer to the MMP1 active site. Coordination of functional conformations at different parts of MMP1 occurs via allosteric communications that can take place via interactions mediated by collagen even if the linker between the domains is absent. Modeling dynamics as a Poisson process enables connecting the picosecond timescales of molecular dynamics simulations with the millisecond timescales of single-molecule measurements. Water-soluble MMP1 interacting with water-insoluble collagen fibrils poses challenges for biochemical studies that the single-molecule tracking can overcome for other insoluble substrates. Interdomain communications are likely important for multidomain proteins.

Citovat

KUMAR, Lokender, Anthony NASH, Chase HARMS, Joan PLANAS IGLESIAS, Derek WRIGHT, Judith KLEIN-SEETHARAMAN a Susanta K SARKAR. Allosteric Communications between Domains Modulate the Activity of Matrix Metalloprotease-1. Biophysical Journal. Bethesda, USA: Biophysical Society, 2020, roč. 119, č. 2, s. 360-374. ISSN 0006-3495. Dostupné z: https://dx.doi.org/10.1016/j.bpj.2020.06.010.

@article{1678778,
   author = {Kumar, Lokender and Nash, Anthony and Harms, Chase and Planas Iglesias, Joan and Wright, Derek and KleinandSeetharaman, Judith and Sarkar, Susanta K},
   article_location = {Bethesda, USA},
   article_number = {2},
   doi = {http://dx.doi.org/10.1016/j.bpj.2020.06.010},
   keywords = {triple-helical collagen; power-law correlations; anisotropic network model; focal cerebral ischemia},
   language = {eng},
   issn = {0006-3495},
   journal = {Biophysical Journal},
   title = {Allosteric Communications between Domains Modulate the Activity of Matrix Metalloprotease-1},
   url = {https://doi.org/10.1016/j.bpj.2020.06.010},
   volume = {119},
   year = {2020}
}

TY  - JOUR
ID  - 1678778
AU  - Kumar, Lokender - Nash, Anthony - Harms, Chase - Planas Iglesias, Joan - Wright, Derek - Klein-Seetharaman, Judith - Sarkar, Susanta K
PY  - 2020
TI  - Allosteric Communications between Domains Modulate the Activity of Matrix Metalloprotease-1
JF  - Biophysical Journal
VL  - 119
IS  - 2
SP  - 360-374
EP  - 360-374
PB  - Biophysical Society
SN  - 00063495
KW  - triple-helical collagen
KW  - power-law correlations
KW  - anisotropic network model
KW  - focal cerebral ischemia
UR  - https://doi.org/10.1016/j.bpj.2020.06.010
L2  - https://doi.org/10.1016/j.bpj.2020.06.010
N2  - An understanding of the structure-dynamics relationship is essential for understanding how a protein works. Prior research has shown that the activity of a protein correlates with intradomain dynamics occurring at picosecond to millisecond timescales. However, the correlation between interdomain dynamics and the function of a protein is poorly understood. Here, we show that communications between the catalytic and hemopexin domains of matrix metalloprotease-1 (MMP1) on type 1 collagen fibrils correlate with its activity. Using single-molecule Forster resonance energy transfer, we identified functionally relevant open conformations in which the two MMP1 domains are well separated, which were significantly absent for catalytically inactive point mutant (E219Q) of MMP1 and could be modulated by an inhibitor or an enhancer of activity. The observed relevance of open conformations resolves the debate about the roles of open and closed MMP1 structures in function. We fitted the histograms of single-molecule Forster resonance energy transfer values to a sum of two Gaussians and the autocorrelations to an exponential and power law. We used a two-state Poisson process to describe the dynamics and calculate the kinetic rates from the fit parameters. All-atom and coarse-grained simulations reproduced some of the experimental features and revealed substrate-dependent MMP1 dynamics. Our results suggest that an interdomain separation facilitates opening up the catalytic pocket so that the collagen chains come closer to the MMP1 active site. Coordination of functional conformations at different parts of MMP1 occurs via allosteric communications that can take place via interactions mediated by collagen even if the linker between the domains is absent. Modeling dynamics as a Poisson process enables connecting the picosecond timescales of molecular dynamics simulations with the millisecond timescales of single-molecule measurements. Water-soluble MMP1 interacting with water-insoluble collagen fibrils poses challenges for biochemical studies that the single-molecule tracking can overcome for other insoluble substrates. Interdomain communications are likely important for multidomain proteins.
ER  -

KUMAR, Lokender, Anthony NASH, Chase HARMS, Joan PLANAS IGLESIAS, Derek WRIGHT, Judith KLEIN-SEETHARAMAN a Susanta K SARKAR. Allosteric Communications between Domains Modulate the Activity of Matrix Metalloprotease-1. \textit{Biophysical Journal}. Bethesda, USA: Biophysical Society, 2020, roč.~119, č.~2, s.~360-374. ISSN~0006-3495. Dostupné z: https://dx.doi.org/10.1016/j.bpj.2020.06.010.

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