6x8o
From Proteopedia
BimBH3 peptide tetramer
Structural highlights
Function[B2L11_HUMAN] Induces apoptosis and anoikis. Isoform BimL is more potent than isoform BimEL. Isoform Bim-alpha1, isoform Bim-alpha2 and isoform Bim-alpha3 induce apoptosis, although less potent than isoform BimEL, isoform BimL and isoform BimS. Isoform Bim-gamma induces apoptosis. Isoform Bim-alpha3 induces apoptosis possibly through a caspase-mediated pathway. Isoform BimAC and isoform BimABC lack the ability to induce apoptosis.[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedBcl-2 proteins orchestrate the mitochondrial pathway of apoptosis, pivotal for cell death. Yet, the structural details of the conformational changes of pro- and antiapoptotic proteins and their interactions remain unclear. Pulse dipolar spectroscopy (double electron-electron resonance [DEER], also known as PELDOR) in combination with spin-labeled apoptotic Bcl-2 proteins unveils conformational changes and interactions of each protein player via detection of intra- and inter-protein distances. Here, we present the synthesis and characterization of pro-apoptotic BimBH3 peptides of different lengths carrying cysteines for labeling with nitroxide or gadolinium spin probes. We show by DEER that the length of the peptides modulates their homo-interactions in the absence of other Bcl-2 proteins and solve by X-ray crystallography the structure of a BimBH3 tetramer, revealing the molecular details of the inter-peptide interactions. Finally, we prove that using orthogonal labels and three-channel DEER we can disentangle the Bim-Bim, Bcl-xL-Bcl-xL, and Bim-Bcl-xL interactions in a simplified interactome. Biophysical Characterization of Pro-apoptotic BimBH3 Peptides Reveals an Unexpected Capacity for Self-Association.,Assafa TE, Nandi S, Smilowicz D, Galazzo L, Teucher M, Elsner C, Putz S, Bleicken S, Robin AY, Westphal D, Uson I, Stoll R, Czabotar PE, Metzler-Nolte N, Bordignon E Structure. 2020 Sep 14. pii: S0969-2126(20)30327-0. doi:, 10.1016/j.str.2020.09.002. PMID:32966763[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
Categories: Large Structures | Czabotar, P E | Robin, A Y | Uson, I | Westphal, D | Apoptosis | Bcl-2 | Bh3 | Bim | Cell death