Anne's paper entitled "Double the Double: Revisiting BCL11B's Multimerization" is published

Fig1: Characterization of the multimerization states and secondary structures of different BCL11B species. (A) Sequence overview of different BCL11B expression constructs and mutants (red) deduced from FRET-FACS experiments. The sequence highlighted in blue denotes the shortest possible construct to form a stable ZF0 fold and was used during MD simulations. Zinc binding residues are shown in gray. (B) Elution profiles from size exclusion chromatography (SEC) of BCL11B42–94 WT (gray), BCL11B42–220 WT (red), and BCL11B42–426 WT (blue). The elution volumes of 1.79 mL (WT), 1.47 mL (220), and 1.57 mL (426) each correspond to calculated stoichiometric factors of 7.0 (WT), 16.6 (220), and 4.0 (426). As SEC data are suitable for a rough estimation of molecular weights and all three constructs appeared as larger complexes than the expected dimers, we continued with crosslinking experiments. (C) Schematic illustration of crosslinking (orange) nearby subunits (cartoon) within higher-order complexes. (D) Reducing 16% tricine SDS-PAGE with crosslinked and control samples of BCL11B42–94 WT and mutants. Circular dichroism spectra of BCL11B42–94 WT in comparison to the mutants (E) BCL11B42–94 I70A, (F) BCL11B42–94 I74A, and (G) BCL11B42–94 K77A, with Zn2+ ions removed or added, respectively.
Fig2: (A–C) Tetrameric structure of the BCL11B54–82 ZF0 CCHC zinc finger domain in cartoon style, highlighting three different core interfaces, including (A) the previously proposed dimer interface (IF-α), (B) the new major β-dimer building block interface (IF-β), stacking the β-sheets of two monomers and stabilized by a salt-bridge K77↔D54, and (C) an additional interface between α-helical regions of two neighboring chains between two β-dimers (IF-γ). (bottom) Corresponding contact probability network for each interface. Nodes display residue IDs labeled with their corresponding one-letter amino acid codes. The thickness and shade of the connecting lines indicate the proportion of time each contact persisted within the main contact-contact principal component analysis (ccPCA) cluster of simulation R2 (Table S1). (D) Schematic illustration of the presumed formation of the BCL11B ZF0 tetramer from four monomeric zinc finger motifs involves multiple stages. Initially, dimers are assembled by joining the sheets of residues D54 to T57 (IF-β) between monomers, building a β-dimer. Next, two β-dimers form a tetramer as a “dimer of dimers” via two emerging hydrophobic interfaces: IF-α, described in our earlier work and an additional interface IF-γ.

BCL11B’s role in cancer may hinge on its unexpected tetramerization. Understanding its structure could be the key to unlocking new therapies...

Anne's paper on "Double the Double: Revisiting BCL11B's Multimerization" is published in PROTEINS. Congratulations Anne!

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