Intrinsically disordered regions influence protein motif usage in Drosophila Ubx and AbdA Hox proteins
Abstract
Hox proteins are evolutionary conserved transcription factors guiding morphogenesis in all bilaterian animals. Conservation mainly concerns the homeodomain (HD), a helix-turn-helix DNA binding motif and flanking sequences close by. Besides, sequences are poorly conserved and disordered. Here we investigate how poorly conserved Intrinsically Disordered Regions (IDRs) influence Hox protein activity, focusing on a closely related Drosophila Hox pair and using a wide range of in vivo function. Studying Drosophila Ultrabithorax (Ubx) and AbdominalA (AbdA) proteins, we find that conserved protein motifs close to the HD are differently used in Ubx and AbdA. Coarse-grained molecular dynamics simulations identify a large set of intra-molecular interactions, notably involving poorly conserved disordered regions upstream and downstream the HD. Swapping these regions in Ubx and AbdA alters protein functions and switches motif dependency in some biological situations. This suggests that IDRs, predicted to mediate large and dynamic sets of intramolecular interactions, influence protein motif usage in a context dependent manner.
Related
- Intrinsically disordered regions navigate DNA replication licensing factors to specific genomic loci.
- Mechanistic Interpretability of Protein Language Models Reveals Encoded Structural and Functional Properties of Intrinsically Disordered Proteins
- Expression of tardigrade intrinsically disordered proteins in C. elegans reveals variable effects on aging and stress
- Molecular dynamics insights into biomineralisation mediated by acidic intrinsically disordered proteins: a case study of molluscan Aspein from the pearl oyster Pinctada fucata
- Single residues within the YTHDF intrinsically disordered region control m6A-dependent mRNA decay
BibTeX
@misc{maurelzaffran2026intrinsically,
title = {{Intrinsically disordered regions influence protein motif usage in Drosophila Ubx and AbdA Hox proteins}},
author = {Corinne Maurel-Zaffran and Ilan Edelstein and Laurianne Michel and Meiggie Macchi and Nathalie Caruso and Andrew Saurin and Yaakov Levy and Yacine Graba},
howpublished = {BioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.09.757964},
url = {https://hal.science/hal-05845160v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Intrinsically disordered regions influence protein motif usage in Drosophila Ubx and AbdA Hox proteins
AU - Corinne Maurel-Zaffran
AU - Ilan Edelstein
AU - Laurianne Michel
AU - Meiggie Macchi
AU - Nathalie Caruso
AU - Andrew Saurin
AU - Yaakov Levy
AU - Yacine Graba
PY - 2026
DA - 2026/10/09
PB - BioRxiv
DO - 10.64898/2026.10.09.757964
UR - https://hal.science/hal-05845160v1
AB - Hox proteins are evolutionary conserved transcription factors guiding morphogenesis in all bilaterian animals. Conservation mainly concerns the homeodomain (HD), a helix-turn-helix DNA binding motif and flanking sequences close by. Besides, sequences are poorly conserved and disordered. Here we investigate how poorly conserved Intrinsically Disordered Regions (IDRs) influence Hox protein activity, focusing on a closely related Drosophila Hox pair and using a wide range of in vivo function. Studying Drosophila Ultrabithorax (Ubx) and AbdominalA (AbdA) proteins, we find that conserved protein motifs close to the HD are differently used in Ubx and AbdA. Coarse-grained molecular dynamics simulations identify a large set of intra-molecular interactions, notably involving poorly conserved disordered regions upstream and downstream the HD. Swapping these regions in Ubx and AbdA alters protein functions and switches motif dependency in some biological situations. This suggests that IDRs, predicted to mediate large and dynamic sets of intramolecular interactions, influence protein motif usage in a context dependent manner.
SN - 2692-8205
ER -