Histone chaperones-structurally diverse, non-catalytic proteins enriched with acidic intrinsically disordered regions (IDRs)-protect histones from spurious nucleic acid interactions and guide their deposition into and out of nucleosomes. Despite their conservation and ubiquity, the function of the chaperone acidic IDRs remains unclear. Here, we show that the Npm2 and Nap1 acidic IDRs are substrates for TTLL4 (Tubulin Tyrosine Ligase Like 4)-catalyzed post-translational glutamate-glutamylation. We demonstrate that to bind, stabilize, and deposit histones into nucleosomes, chaperone acidic IDRs function as DNA mimetics. Our biochemical, computational, and biophysical studies reveal that glutamylation of these chaperone polyelectrolyte acidic stretches functions to enhance DNA electrostatic mimicry, promoting the binding and stabilization of H2A/H2B heterodimers and facilitating nucleosome assembly. This discovery provides insights into both the previously unclear function of the acidic IDRs and the regulatory role of post-translational modifications in chromatin dynamics.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10987829 | PMC |
| http://dx.doi.org/10.1016/j.isci.2024.109458 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
TANDEM ZINC-FINGER/PLUS3: a multifaceted integrator of light signaling.
Trends Plant Sci
December 2024
School of Molecular Biosciences, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK. Electronic address:
TANDEM ZINC-FINGER/PLUS3 (TZP) is a nuclear-localized protein with multifaceted roles in modulating plant growth and development under diverse light conditions. The unique combination of two intrinsically disordered regions (IDRs), two zinc-fingers (ZFs), and a PLUS3 domain provide a platform for interactions with the photoreceptors phytochrome A (phyA) and phyB, light signaling components, and nucleic acids. TZP controls flowering and hypocotyl elongation by regulating gene expression and protein abundance in a blue, red, or far-red light-specific context.
View Article and Find Full Text PDFIn the Beginning: Let Hydration Be Coded in Proteins for Manifestation and Modulation by Salts and Adenosine Triphosphate.
Int J Mol Sci
November 2024
Department of Biological Sciences, Faculty of Science, National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260, Singapore.
Water exists in the beginning and hydrates all matter. Life emerged in water, requiring three essential components in compartmentalized spaces: (1) universal energy sources driving biochemical reactions and processes, (2) molecules that store, encode, and transmit information, and (3) functional players carrying out biological activities and structural organization. Phosphorus has been selected to create adenosine triphosphate (ATP) as the universal energy currency, nucleic acids for genetic information storage and transmission, and phospholipids for cellular compartmentalization.
View Article and Find Full Text PDFConservation of function without conservation of amino acid sequence in intrinsically disordered transcriptional activation domains.
bioRxiv
December 2024
Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, 94720.
Protein function is canonically believed to be more conserved than amino acid sequence, but this idea is only well supported in folded domains, where highly diverged sequences can fold into equivalent 3D structures. In contrast, intrinsically disordered protein regions (IDRs) do not fold into a stable 3D structure, thus it remains unknown when and how function is conserved for IDRs that experience rapid amino acid sequence divergence. As a model system for studying the evolution of IDRs, we examined transcriptional activation domains, the regions of transcription factors that bind to coactivator complexes.
View Article and Find Full Text PDFThe strand exchange domain of tumor suppressor PALB2 is intrinsically disordered and promotes oligomerization-dependent DNA compaction.
iScience
December 2024
Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St Louis, MO, USA.
The partner and localizer of BRCA2 (PALB2) is a scaffold protein linking BRCA1 with BRCA2 and RAD51 during homologous recombination (HR). PALB2 interaction with DNA strongly enhances HR in cells, while the PALB2 DNA-binding domain (PALB2-DBD) supports DNA strand exchange . We determined that PALB2-DBD is intrinsically disordered beyond a single N-terminal α-helix.
View Article and Find Full Text PDFEvolutionary analysis of ZAP and its cofactors identifies intrinsically disordered regions as central elements in host-pathogen interactions.
Comput Struct Biotechnol J
December 2024
Scientific Institute IRCCS E. MEDEA, Computational Biology Unit, Bosisio Parini 23842, Italy.
Article Synopsis
- The zinc-finger antiviral protein (ZAP) plays a crucial role in innate immunity by targeting non-self nucleic acids, interacting with cofactors like TRIM25, Riplet, and KHNYN to exert its antiviral effects.
- An analysis of ZAP and its cofactors across four mammalian groups showed signs of positive selection, indicating rapid evolutionary change, particularly in intrinsically disordered regions (IDRs) that evolve faster than the structured parts of the proteins.
- The study suggests that phase separation (PS) may be linked to the antiviral functions of ZAP and its cofactors, with positively selected sites in these regions highlighting their importance in the ongoing evolutionary battle between hosts and viruses.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!