Birthe B. Kragelund

Proteoform plasticity modulates the temperature response in circadian timekeeping

Jacqueline F. Pelham, Alex T. Keeley, Emery T. Usher, Jacob H. Martinsen et autres

Abstract The molecular circadian clock optimally coordinates an organism’s physiology with the light/dark cycle. One commonality among circadian molecular clock proteins is that they undergo alternative splicing, yielding multiple proteoforms. The isoform-specific sequences spliced into clock proteins contain intrinsically disordered regions (IDRs), …

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Autoinhibition of untimely DNA binding by structural disorder in the full-length peroxisome proliferator-activated receptors (PPARs)

Milena R. Lalic, Elisabeth G. K. Thomsen, F. Emil Thomasen, Aditya Udupa et autres

Structural disorder in nuclear receptors is essential for gene transcription, but mechanisms are lacking. Using experiment and computation, including residue-resolution NMR, we demonstrate how structural disorder in full-length peroxisome proliferator-activated receptors (PPARs) contributes to function. We show that the disordered AB domain …

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Integrative structural analysis of human endosomal NHE6 reveals a lipid-associated gate and disordered C-terminus

Lukas P. Feilen, Lara Kristin Sach, Emil E. Tranchant, Milena R. Lalic et autres

Human NHE6 (HsNHE6) is an endosomal Na⁺/H⁺ exchanger essential for maintaining luminal pH and endo-lysosomal trafficking in neurons. HsNHE6 mutations are implicated in devastating neurological syndromes, but mechanistically the transporter remains poorly understood. Here, we present the single-particle cryo-electron microscopy (cryo-EM) structure …

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Integrative structural analysis of human endosomal NHE6 reveals a lipid-associated gate and disordered C-terminus.

Lukas P. Feilen, Lara Kristin Sach, Emil E. Tranchant, Milena R. Lalic et autres

, with kinetic analysis revealing a preference for K⁺. A structured C-terminal helix interacts with the transmembrane core, jointly forming a hydrophobic cavity containing two non-protein cryo-EM densities consistent with bound lipids that may modulate cation access to the ion-binding site. The …

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The RecBCD complex interacts directly with the DNA sliding clamp in Escherichia coli.

Ida Mathilde Marstein Riisnæs, Synnøve Brandt Ræder, Signe Simonsen, Krister Vikedal et autres

DNA sliding clamps are central coordinators of genome replication and maintenance, yet the full binding network ("interactome") of the bacterial β-clamp remains incompletely defined. Here, we report a novel interaction between Escherichia coli β-clamp and the helicase-nuclease RecBCD complex. Using bacterial two-hybrid …

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The RecBCD complex interacts directly with the DNA sliding clamp in Escherichia coli

Ida Mathilde Marstein Riisnæs, Synnøve Brandt Ræder, Signe Simonsen, Krister Vikedal et autres

ABSTRACT DNA sliding clamps are essential coordinators of genome replication and maintenance across all domains of life and serve as platforms for recruiting diverse binding partners. The bacterial DNA sliding clamp, β-clamp, functions analogous to the eukaryotic proliferating cell nuclear antigen (PCNA), …

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Metal-binding properties of the N-terminal intrinsically disordered region of the membrane protein PcoB involved in bacterial copper homeostasis

Hugo Bâlon, Simon Rouxhet, Julien Mignon, Marylène Vandevenne et autres

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Proteasomal control of transcription factors: mechanisms, regulation and dysregulation

Fia B. Larsen, Birthe B. Kragelund, Kresten Lindorff-Larsen, Pétur O. Heidarsson et autres

Regulation of transcription is of key importance for essentially all aspects of biology. Accordingly, transcription factors (TFs) are often subject to rapid degradation, which in turn allows for strict regulation of gene expression and prevents uncontrolled activation or repression of target genes. …

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Stability and interaction defects in the Sin3A-PAH1 αα-hub domain associated with loss-of-function variants

Amanda D. Due, Sigrid Jørsboe, Louise T. Jensen, Charlotte O’Shea et autres

Hub proteins organize large interactomes using their hub domains for protein–protein interactions. αα-hub domains are present in transcriptional regulators, such as Switch-insensitive 3A (Sin3A), an integral scaffolding protein of histone deacetylation complexes. Here, we relate αα-hub stability to function by structural and …

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Targeting of Kaposi’s sarcoma-associated herpesvirus by immunotoxins directed against the viral G protein-coupled receptor, ORF74

Dagmar Fæster Kildedal, Anna Drzazga, Anjali Sharma, Christian Berg et autres

BACKGROUND AND PURPOSE: Kaposi's sarcoma-associated herpesvirus (KSHV) is a common virus with severe outcome and no effective antiviral treatment. KSHV encodes the constitutive active chemokine receptor ORF74 with broad-spectrum CXC-chemokine binding. Here, we leverage ORF74's mimic of endogenous receptors to design chemokine-based …

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Chemical Shift Assignments for Small Hydrophobic (SH) protein residues 39-57

Kira Devantier, Birthe B. Kragelund

Chemical Shift Assignments for Small Hydrophobic (SH) protein residues 2-12

Kira Devantier, Birthe B. Kragelund