ROLE OF CHARGE TRANSFER IN THE ACTIVATION OF PRO-APOPTOTIC
REGULATORS BAX AND BAK

k 2012

ROLE OF CHARGE TRANSFER IN THE ACTIVATION OF PRO-APOPTOTIC REGULATORS BAX AND BAK

IONESCU, Crina-Maria; Radka SVOBODOVÁ VAŘEKOVÁ; Heinrich J HUBER a Jaroslav KOČA

Základní údaje

Originální název

ROLE OF CHARGE TRANSFER IN THE ACTIVATION OF PRO-APOPTOTIC REGULATORS BAX AND BAK

Autoři

IONESCU, Crina-Maria; Radka SVOBODOVÁ VAŘEKOVÁ; Heinrich J HUBER a Jaroslav KOČA

Vydání

XXIII. biochemický sjezd České společnosti pro biochemii a molekulární biologii a Slovenské spoločnosti pre biochémiu a molekulárnu biológiu, 2012

Další údaje

Typ výsledku

Prezentace na konferencích

Utajení

není předmětem státního či obchodního tajemství

Označené pro přenos do RIV

Klíčová slova anglicky

apoptosis, allostery, charge transfer

Změněno: 18. 9. 2012 15:32, Mgr. Ing. Crina-Maria Ionescu, Ph.D.

Anotace

V originále

The activation of the proteins Bak and Bax is essential for programmed cell death (apoptosis) [1]. When activated, Bax and Bak homo-oligomerize and form pores in the mitochondrial outer membrane, causing the release of proteins that execute cell death. Yet, it is unknown precisely how Bak and Bax activation leads to their oligomerization, and what biophysical processes lead to a change in their structure and function [2]. A better understanding of these processes would help to design better drugs for overcoming apoptosis resistance in cancer, or for mitigating hypersensitive apoptosis during neuro-degenerative and auto-immune diseases. We investigated the role of charge transfer for the process of Bak and Bax activation by employing a method to calculate atomic charges of quantum chemical quality in proteins [3]. We identified a charge transfer network that conveys activation information from the Bax activation site to the well distanced sites required for Bax oligomerization. Our results confirm ongoing speculations of allosteric sensing during Bax activation, and reveal that allosteric regulation in Bax is mediated by charge transfer. Moreover, we found that such a charge transfer network is also plausible in Bak. Finally, our charge profile analysis identified new structural elements in Bax and Bak that represent novel targets for modulating apoptosis. We discuss these results here, and show how a straightforward analysis based on atomic point charges can be correlated with biological investigations.

Návaznosti

GD301/09/H004, projekt VaV

Název: Molekulární a strukturní biologie vybraných cytostatik. Od mechanistických studií k chemoterapii rakoviny

Investor: Grantová agentura ČR, Molekulární a strukturní biologie vybraných cytostatik. Od mechanických studií k chemoterapii rakoviny

Citovat

IONESCU, Crina-Maria; Radka SVOBODOVÁ VAŘEKOVÁ; Heinrich J HUBER a Jaroslav KOČA. ROLE OF CHARGE TRANSFER IN THE ACTIVATION OF PRO-APOPTOTIC REGULATORS BAX AND BAK. In XXIII. biochemický sjezd České společnosti pro biochemii a molekulární biologii a Slovenské spoločnosti pre biochémiu a molekulárnu biológiu. 2012.

@proceedings{992728,
   author = {Ionescu, CrinaandMaria and Svobodová Vařeková, Radka and Huber, Heinrich J and Koča, Jaroslav},
   booktitle = {XXIII. biochemický sjezd České společnosti pro biochemii a molekulární biologii a Slovenské spoločnosti pre biochémiu a molekulárnu biológiu},
   keywords = {apoptosis, allostery, charge transfer},
   title = {ROLE OF CHARGE TRANSFER IN THE ACTIVATION OF PRO-APOPTOTIC REGULATORS BAX AND BAK},
   year = {2012}
}

TY  - CONF
ID  - 992728
AU  - Ionescu, Crina-Maria - Svobodová Vařeková, Radka - Huber, Heinrich J - Koča, Jaroslav
PY  - 2012
TI  - ROLE OF CHARGE TRANSFER IN THE ACTIVATION OF PRO-APOPTOTIC REGULATORS BAX AND BAK
KW  - apoptosis, allostery, charge transfer
N2  - The activation of the proteins Bak and Bax is essential for programmed cell death (apoptosis) [1]. When activated, Bax and Bak homo-oligomerize and form pores in the mitochondrial outer membrane, causing the release of proteins that execute cell death. Yet, it is unknown precisely how Bak and Bax activation leads to their oligomerization, and what biophysical processes lead to a change in their structure and function [2]. A better understanding of these processes would help to design better drugs for overcoming apoptosis resistance in cancer, or for mitigating hypersensitive apoptosis during neuro-degenerative and auto-immune diseases. We investigated the role of charge transfer for the process of Bak and Bax activation by employing a method to calculate atomic charges of quantum chemical quality in proteins [3]. We identified a charge transfer network that conveys activation information from the Bax activation site to the well distanced sites required for Bax oligomerization. Our results confirm ongoing speculations of allosteric sensing during Bax activation, and reveal that allosteric regulation in Bax is mediated by charge transfer. Moreover, we found that such a charge transfer network is also plausible in Bak. Finally, our charge profile analysis identified new structural elements in Bax and Bak that represent novel targets for modulating apoptosis. We discuss these results here, and show how a straightforward analysis based on atomic point charges can be correlated with biological investigations.
ER  -

IONESCU, Crina-Maria; Radka SVOBODOVÁ VAŘEKOVÁ; Heinrich J HUBER a Jaroslav KOČA. ROLE OF CHARGE TRANSFER IN THE ACTIVATION OF PRO-APOPTOTIC REGULATORS BAX AND BAK. In \textit{XXIII. biochemický sjezd České společnosti pro biochemii a molekulární biologii a Slovenské spoločnosti pre biochémiu a molekulárnu biológiu}. 2012.

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