Sandbox Reserved 1122: Difference between revisions
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The tertiary structure of Bcl-2 shows that this protein contains a hydrophobic groove made of the BH1, BH2 and BH3 domains on its surface that allows dimerization with other members of the Bcl-2 family. This region needs to be highly conserved to keep the ability of interacting with the BH3 domain of the proapoptotic protein of the family, in fact, it has been shown that a mutation in this structure leads to the silencing of the dimerization thus may inhibit the activity of Bcl-2. The isoform 1 and 2 differs from two amino acid in the hydrophobic groove but this difference doesn’t induce any change in the conformation of this protein. However as expected, it affects the affinity with Bad and Bak proteins (from the Bcl-2 family). Indeed Bcl-2 isoform 1 shows to have a weaker affinity for Bad and Bak compared to isoform 2.<ref>[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC30598/ Solution structure of the antiapoptotic protein bcl-2]</ref> | The tertiary structure of Bcl-2 shows that this protein contains a hydrophobic groove made of the BH1, BH2 and BH3 domains on its surface that allows dimerization with other members of the Bcl-2 family. This region needs to be highly conserved to keep the ability of interacting with the BH3 domain of the proapoptotic protein of the family, in fact, it has been shown that a mutation in this structure leads to the silencing of the dimerization thus may inhibit the activity of Bcl-2. The isoform 1 and 2 differs from two amino acid in the hydrophobic groove but this difference doesn’t induce any change in the conformation of this protein. However as expected, it affects the affinity with Bad and Bak proteins (from the Bcl-2 family). Indeed Bcl-2 isoform 1 shows to have a weaker affinity for Bad and Bak compared to isoform 2.<ref>[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC30598/ Solution structure of the antiapoptotic protein bcl-2]</ref> | ||
Moreover, Glycine 145 in the BH1 domain and Tryptophane 188 in the BH2 domain of Bcl-2 are also clue residues for the interaction between the hydrophobic pocket and the BH3 domain of the partner. In fact it has been shown that a mutation of one of these two amino acids suppress such interaction.<ref>[https://books.google.fr/books?id=WhwvPX0K2BMC&pg=PA36&lpg=PA36&dq=bcl-2+isoform+1+electrostatic+potential&source=bl&ots=y3NzAJJIuV&sig=hlbn50xllAZ7fArKAODsypZZD1A&hl=fr&sa=X&ved=0ahUKEwjS88_0ztHKAhWH0hoKHddyAdIQ6AEIQTAD#v=onepage&q=bcl-2%20isoform%201%20electrostatic%20potential&f=false | |||
Essentials of Apoptosis : A Guide for Basic and Clinical Research Editors: Yin, Xiao-Ming, Dong, Zheng (Eds.)]</ref> | |||
== Function == | == Function == | ||
