6yld

Crystal structure of Trichoplax adhaerens trBcl-2L2 bound to trBak BH3

spinqualitylabelsall models 6yld, resolution 1.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6yld is a 4 chain structure with sequence from Trichoplax sp. H2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.4Å Ligands: EDO, TAR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A369S2N9_9METZ Publication Abstract from PubMed In metazoans, Bcl-2 family proteins are major regulators of mitochondrially mediated apoptosis; however, their evolution remains poorly understood. Here, we describe the molecular characterization of the four members of the Bcl-2 family in the most primitive metazoan, Trichoplax adhaerens All four trBcl-2 homologs are multimotif Bcl-2 group, with trBcl-2L1 and trBcl-2L2 being highly divergent antiapoptotic Bcl-2 members, whereas trBcl-2L3 and trBcl-2L4 are homologs of proapoptotic Bax and Bak, respectively. trBax expression permeabilizes the mitochondrial outer membrane, while trBak operates as a BH3-only sensitizer repressing antiapoptotic activities of trBcl-2L1 and trBcl-2L2. The crystal structure of a trBcl-2L2:trBak BH3 complex reveals that trBcl-2L2 uses the canonical Bcl-2 ligand binding groove to sequester trBak BH3, indicating that the structural basis for apoptosis control is conserved from T. adhaerens to mammals. Finally, we demonstrate that both trBax and trBak BH3 peptides bind selectively to human Bcl-2 homologs to sensitize cancer cells to chemotherapy treatment. Ancient and conserved functional interplay between Bcl-2 family proteins in the mitochondrial pathway of apoptosis.,Popgeorgiev N, Sa JD, Jabbour L, Banjara S, Nguyen TTM, Akhavan-E-Sabet A, Gadet R, Ralchev N, Manon S, Hinds MG, Osigus HJ, Schierwater B, Humbert PO, Rimokh R, Gillet G, Kvansakul M Sci Adv. 2020 Sep 30;6(40):eabc4149. doi: 10.1126/sciadv.abc4149. Print 2020 Sep. PMID:32998881 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also B-cell lymphoma proteins 3D structures

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