7OFM
NMR structure of the Bak transmembrane helix in DPC micelles
Summary for 7OFM
| Entry DOI | 10.2210/pdb7ofm/pdb |
| NMR Information | BMRB: 34621 |
| Descriptor | Bcl-2 homologous antagonist/killer (1 entity in total) |
| Functional Keywords | mitochondria, pore formation, bcl2 proteins, apoptosis |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 3244.94 |
| Authors | Sperl, L.E.,Hagn, F. (deposition date: 2021-05-05, release date: 2021-06-23, Last modification date: 2024-06-19) |
| Primary citation | Sperl, L.E.,Ruhrnossl, F.,Schiller, A.,Haslbeck, M.,Hagn, F. High-resolution analysis of the conformational transition of pro-apoptotic Bak at the lipid membrane. Embo J., 40:e107159-e107159, 2021 Cited by PubMed Abstract: Permeabilization of the outer mitochondrial membrane by pore-forming Bcl2 proteins is a crucial step for the induction of apoptosis. Despite a large set of data suggesting global conformational changes within pro-apoptotic Bak during pore formation, high-resolution structural details in a membrane environment remain sparse. Here, we used NMR and HDX-MS (Hydrogen deuterium exchange mass spectrometry) in lipid nanodiscs to gain important high-resolution structural insights into the conformational changes of Bak at the membrane that are dependent on a direct activation by BH3-only proteins. Furthermore, we determined the first high-resolution structure of the Bak transmembrane helix. Upon activation, α-helix 1 in the soluble domain of Bak dissociates from the protein and adopts an unfolded and dynamic potentially membrane-bound state. In line with this finding, comparative protein folding experiments with Bak and anti-apoptotic BclxL suggest that α-helix 1 in Bak is a metastable structural element contributing to its pro-apoptotic features. Consequently, mutagenesis experiments aimed at stabilizing α-helix 1 yielded Bak variants with delayed pore-forming activity. These insights will contribute to a better mechanistic understanding of Bak-mediated membrane permeabilization. PubMed: 34523144DOI: 10.15252/embj.2020107159 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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