Chloride Intracellular Channel Protein 2: Difference between revisions

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Student, Céline Debarnot, David Canner, Eran Hodis, Michal Harel, Alexander Berchansky

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 The  <scene name='Sandbox123/C-term_clic2/1'>C-terminal domain</scene>(residues 107-245) is exclusively helical composed. It contains a long loop (residues 152-180) between helices 5 and 6, which is a characteristic of the CLIC family wich is called the <scene name='Sandbox123/Foot_loop/1'>foot loop</scene>.
 Those two domains are linked by an interdomain loop (residues 95–106) rich in proline residues (more than 33% of proline). Actually there are
-<scene name='Sandbox123/Two_diprolines/1'>two diproline</scene>, Pro70-Pro71 and Pro96-Pro97 in this loop wich is called <scene name='Sandbox123/Joint_loop/2'>joint loop</scene>. Those diprolines lead to direction changing in the peptide chain. The largest deviations in the N-terminal domain occurs between the residues 55 and 69 that implies helix α2 and its surrounding sequences and also a loop (residues 80-84) that bind the β-strand 4 to helix α3. Crystallographic studies gave two forms of CLIC2, on each one we found out that this protein contain a right handed hook conformation. In fact, the long loop between helices 5 and 6 protrudes on the surface.
+<scene name='Sandbox123/Proline/1'>two di proline</scene>, Pro70-Pro71 and Pro96-Pro97 in this loop wich is called <scene name='Sandbox123/Joint_loop/2'>joint loop</scene>. Those diprolines lead to direction changing in the peptide chain. The largest deviations in the N-terminal domain occurs between the residues 55 and 69 that implies helix α2 and its surrounding sequences and also a loop (residues 80-84) that bind the β-strand 4 to helix α3. Crystallographic studies gave two forms of CLIC2, on each one we found out that this protein contain a right handed hook conformation. In fact, the long loop between helices 5 and 6 protrudes on the surface.
 Finally, something that we have to highlight is the fact that this protein presents an intramolecular disulfide bridge. It is a well resolved disulfide bond between<scene name='Sandbox123/Disulfide_bond/2'>Cys30 and Cys33</scene> on the N-terminal of helix 1 thanks to a CXXC motif. The Cys 30 is exposed to the cavity between the N- and the C-terminal domains, which means that this cystein is reachable by other molecules. On the opposite, the Cys 33 is located one turn after the Cys 30, thus is buried inside the N-terminal domain. Let us notice that the partial positive charge present on the N-terminal end of helix increases the nucleophility of the thiol group of the Cys 30, which is a characteristic of protein belonging to the glutaredoxin family. On another hand, we would like to point out the fact that this intramolecular disulfide bridge is the reason why CLIC2 is the only CLIC protein that exists only in the monomer form. In CLIC1, there is no intramolecular disulfide bridge in its monomer state but only in its dimer state where the bound is established between Cys 24 of the first CLIC1 and Cys 59 of the second one. Actually, this bridge is responsible for the dimerisation. In analogy, the corresponding residues in CLIC2 are Cys 30 and Ala 65; consequently, there is no possibility to establish a disulfide bridge. An experiment has been performed to check if CLIC2 cannot dimerise: mutant has been made in which Cys had been settled at the appropriate positions instead of Ala 65. Even in reducing conditions, no disulfide bridge can be created. That means that up to now, CLIC2 remains as a non dimerisable protein.