Sandbox Reserved 973: Difference between revisions

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The pacemaker of the circadian system is the suprachiamastic nucleus (SNC) located in the hypothalamus. This center controls the circadian rhythm through the coordination of peripheric oscillators all over the organism. The mechanisms that occur in the peripheric system are, at a molecular level, very similar to those in the SNC; that is to say a network of transcriptional and translational regulations, creating different loops that take about 24 hours to complete. This circadian cycle regulates many physiologic parameters and coordonates several phenomenon such as sleep period or hormon levels. One one the most important protein in this rhythm is the heterodimeric complex CLOCK:BMAL1, which is a transcriptionnal factor responseable for the activation of 2 type of genes; Period(Per1,Per2) and Cryptochrome(Cry1,Cry2), by interacting with the E-box DNA. In deed mutants mice devoid of CLOCK or BMAL1 proteins have seriously disrupted rhythm, at a molecular level as well as on the behavioural one.

The two peptides involved in the dimere have very similar sequences . In ''mus musculus'' ~~BMAL1 is 387 residues long and CLOCK is 361~~.

The two peptides involved in the dimere have very similar sequences . The structure of CLOCK and BMAL1 have mostly been studied in ''mus musculus''. Both of these subunits are basic helix-loop-helix-PAS proteins (bHLH-PAS) which contain the same 3 particular domains: a bHLH domain, a PAS-A domain and a PAS-B domain, plus a transactivator domain in the C-terminal region. They are involved in DNA binding and dimerization abilities. Mutations that affects the heterodimer interfaces can then disturb the activity of the complex and therefore the persistence and periodicity of the circadian cycle. In deed the two subunits are tightly intertwined as each domain of CLOCK interact with the corresponding one of BMAL1.

Both of these subunits are basic helix-loop-helix-PAS proteins (bHLH-PAS) which contain the same 3 particular domains: a bHLH domain, a PAS-A domain and a PAS-B domain. They are involved in DNA binding and dimerization abilities. Mutations that affects the heterodimer interfaces can then disturb the activity of the complex and therefore the persistence and periodicity of the circadian cycle. In deed the two subunits are tightly intertwined as each domain of CLOCK interact with the corresponding one of BMAL1.

Another important feature of this heterodimere is that there is an assymetric distribution of the electrostatic potential. CLOCK tends to have a global negative charge while BMAL1 has a positive one. The fact that the two subunits of the complex expose this charged surface in the 3D structure match with the hypothesis that CLOCK and BMAL1 are not involved in the same interaction with the other regulatory proteins listed before.

Sandbox Reserved 973: Difference between revisions

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 The pacemaker of the circadian system is the suprachiamastic nucleus (SNC) located in the hypothalamus. This center controls the circadian rhythm through the coordination of peripheric oscillators all over the organism. The mechanisms that occur in the peripheric system are, at a molecular level, very similar to those in the SNC; that is to say a network of transcriptional and translational regulations, creating different loops that take about 24 hours to complete. This circadian cycle regulates many physiologic parameters and coordonates several phenomenon such as sleep period or hormon levels. One one the most important protein in this rhythm is the heterodimeric complex CLOCK:BMAL1, which is a transcriptionnal factor responseable for the activation of 2 type of genes; Period(Per1,Per2) and Cryptochrome(Cry1,Cry2), by interacting with the E-box DNA. In deed mutants mice devoid of CLOCK or BMAL1 proteins have seriously disrupted rhythm, at a molecular level as well as on the behavioural one.
-The two peptides involved in the dimere have very similar sequences . In ''mus musculus'' BMAL1 is 387 residues long and CLOCK is 361.
+The two peptides involved in the dimere have very similar sequences . The structure of CLOCK and BMAL1 have mostly been studied in ''mus musculus''. Both of these subunits are basic helix-loop-helix-PAS proteins (bHLH-PAS) which contain the same 3 particular domains: a bHLH domain, a PAS-A domain and a PAS-B domain, plus a transactivator domain in the C-terminal region. They are involved in DNA binding and dimerization abilities. Mutations that affects the heterodimer interfaces can then disturb the activity of the complex and therefore the persistence and periodicity of the circadian cycle. In deed the two subunits are tightly intertwined as each domain of CLOCK interact with the corresponding one of BMAL1.
-Both of these subunits are basic helix-loop-helix-PAS proteins (bHLH-PAS) which contain the same 3 particular domains: a bHLH domain, a PAS-A domain and a PAS-B domain. They are involved in DNA binding and dimerization abilities. Mutations that affects the heterodimer interfaces can then disturb the activity of the complex and therefore the persistence and periodicity of the circadian cycle. In deed the two subunits are tightly intertwined as each domain of CLOCK interact with the corresponding one of BMAL1.
 Another important feature of this heterodimere is that there is an assymetric distribution of the electrostatic potential. CLOCK tends to have a global negative charge while BMAL1 has a positive one. The fact that the two subunits of the complex expose this charged surface in the 3D structure match with the hypothesis that CLOCK and BMAL1 are not involved in the same interaction with the other regulatory proteins listed before.