Sandbox Reserved 973: Difference between revisions

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== Domains ==

bHLH domains are especially composed by 2 C-terminal helices called 1 and 2 that are involved in the formation of a canonical four-helical bHLH bundle. This bond between the HLH domains helps to stabilize the heterodimeric complex as the core of the the bundle is very hydrophobic. The spatial arrangement of this assembly has a major role in the the E-box recognition. The 1 helices are responseable for the DNA binding and the aminoacid sequence

PAS-A domains don't have the same conformation in the two subunits. In BMAL1, we can observe 3 loops involving about 60 residues whereas in CLOCK there are only 25 residues in a single loop. Nevertheless, this two PAS-A domains adopt a typical PAS fold. The core of these domains contains a five-stranded antiparallel β sheet (AβBβGβHβIβ) as well as numerous α helices (Cα, DαEαFα). They also contain an N-terminal A'α helix that does not belong to the canonical PAS fold. Those helices pack in between the β-sheet faces and are involved in the dimerization interactions.

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in both subunits the tow PAS domains are linked thanks to an ADN linker of approximately 15 residues called L2 but the conformation of this linker is very different.

In CLOCK the main part of L2 is buried between the dimeric interface whereas in BMAL1 the linker is exposed on the outside and is very flexible. The PAS-B domaines are stacked in a parallel way. The sheet of BMAL1 contacts the helical face of CLOCK so several residues get hidden on CLOCK as well as on BMAL1, including Tyr310, Val315, Leu318 of the first one and Phe423, Trp427 and Val435 of the second one. Hydrophobic interactions are once more involved in the dimerization process. As an exemple, BMAL1 Trp427 located in the -sheet intrudes in a hydrophobic cleft created by the CLOCK helical face fold.

In CLOCK the main part of L2 is buried between the dimeric interface whereas in BMAL1 the linker is exposed on the outside and is very flexible. The PAS-B domaines are stacked in a parallel way. The sheet of BMAL1 contacts the helical face of CLOCK so several residues get hidden on CLOCK as well as on BMAL1, including Tyr310, Val315, Leu318 of the first one and Phe423, Trp427 and Val435 of the second one. Hydrophobic interactions are once more involved in the dimerization process. As an exemple, BMAL1 Trp427 located in the -sheet intrudes in a hydrophobic cleft created by the CLOCK helical face fold, where il contacts the indole ring of CLOCK Trp248.

Sandbox Reserved 973: Difference between revisions

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@@ Line 13: / Line 13: @@
 == Domains ==
+bHLH domains are especially composed by 2 C-terminal helices called 1 and 2 that are involved in the formation of a canonical four-helical bHLH bundle. This bond between the HLH domains helps to stabilize the heterodimeric complex as the core of the the bundle is very hydrophobic. The spatial arrangement of this assembly has a major role in the the E-box recognition. The 1 helices are responseable for the DNA binding and the aminoacid sequence
 PAS-A domains don't have the same conformation in the two subunits. In BMAL1, we can observe 3 loops involving about 60 residues whereas in CLOCK there are only 25 residues in a single loop. Nevertheless, this two PAS-A domains adopt a typical PAS fold. The core of these domains contains a five-stranded antiparallel β sheet (AβBβGβHβIβ) as well as numerous α helices (Cα, DαEαFα). They also contain an N-terminal A'α helix that does not belong to the canonical PAS fold. Those helices pack in between the β-sheet faces and are involved in the dimerization interactions.
@@ Line 19: / Line 21: @@
 in both subunits the tow PAS domains are linked thanks to an ADN linker of approximately 15 residues called L2 but the conformation of this linker is very different.
-In CLOCK the main part of L2 is buried between the dimeric interface whereas in BMAL1 the linker is exposed on the outside and is very flexible. The PAS-B domaines are stacked in a parallel way. The sheet of BMAL1 contacts the helical face of CLOCK so several residues get hidden on CLOCK as well as on BMAL1, including Tyr310, Val315, Leu318 of the first one and Phe423, Trp427 and Val435 of the second one. Hydrophobic interactions are once more involved in the dimerization process. As an exemple, BMAL1 Trp427 located in the -sheet intrudes in a hydrophobic cleft created by the CLOCK helical face fold.
+In CLOCK the main part of L2 is buried between the dimeric interface whereas in BMAL1 the linker is exposed on the outside and is very flexible. The PAS-B domaines are stacked in a parallel way. The sheet of BMAL1 contacts the helical face of CLOCK so several residues get hidden on CLOCK as well as on BMAL1, including Tyr310, Val315, Leu318 of the first one and Phe423, Trp427 and Val435 of the second one. Hydrophobic interactions are once more involved in the dimerization process. As an exemple, BMAL1 Trp427 located in the -sheet intrudes in a hydrophobic cleft created by the CLOCK helical face fold, where il contacts the indole ring of CLOCK Trp248.