9GR9

Homodimer of BACH1 BTB domain

Summary for 9GR9

• Entry DOI: 10.2210/pdb9gr9/pdb
• Related: 8S7D 8S7E 9GP5
• Descriptor: Transcription regulator protein BACH1 (2 entities in total)
• Functional Keywords: bach1, back-to-back domain, btb domain, dna binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 56232.14

Authors

Gutmann, S.,Hinniger, A.,Berneiser, K.,Goretzki, B. (deposition date: 2024-09-11, release date: 2024-12-11, Last modification date: 2025-07-02)

Primary citation

Goretzki, B.,Khoshouei, M.,Schroder, M.,Penner, P.,Egger, L.,Stephan, C.,Argoti, D.,Dierlamm, N.,Rada, J.M.,Kapps, S.,Muller, C.S.,Thiel, Z.,Mutlu, M.,Tschopp, C.,Furkert, D.,Freuler, F.,Haenni, S.,Tenaillon, L.,Knapp, B.,Hinniger, A.,Hoppe, P.,Schmidt, E.,Gutmann, S.,Iurlaro, M.,Ryzhakov, G.,Fernandez, C.
Dual BACH1 regulation by complementary SCF-type E3 ligases.
Cell, 187:7585-7602.e25, 2024

PubMed Abstract: Broad-complex, tramtrack, and bric-à-brac domain (BTB) and CNC homolog 1 (BACH1) is a key regulator of the cellular oxidative stress response and an oncogene that undergoes tight post-translational control by two distinct F-box ubiquitin ligases, SCF and SCF. However, how both ligases recognize BACH1 under oxidative stress is unclear. In our study, we elucidate the mechanism by which FBXO22 recognizes a quaternary degron in a domain-swapped β-sheet of the BACH1 BTB dimer. Cancer-associated mutations and cysteine modifications destabilize the degron and impair FBXO22 binding but simultaneously expose an otherwise shielded degron in the dimer interface, allowing FBXL17 to recognize BACH1 as a monomer. These findings shed light on a ligase switch mechanism that enables post-translational regulation of BACH1 by complementary ligases depending on the stability of its BTB domain. Our results provide mechanistic insights into the oxidative stress response and may spur therapeutic approaches for targeting oxidative stress-related disorders and cancer.

PubMed: 39657677
DOI: 10.1016/j.cell.2024.11.006

Experimental method

X-RAY DIFFRACTION (2.25 Å)