In Silico Structure-Based Interactomic Analysis of the Scaffolding Protein DCAF7
Abstract
WD40 domains share a widespread β-propeller fold, and often act as versatile scaffold proteins. Despite their central role in organizing dynamic cellular complexes, the molecular and structural mechanisms of many WD40 proteins remain poorly understood. Among them, DCAF7, an ubiquitously expressed and essential gene in human, also encodes a highly conserved WD40 protein in eukaryotic organisms. It is known to interact with multiple and functionnally diverse partners to coordinates cellular activity of several protein kinases as well as transcriptional regulators, thereby modulating key cellular processes such as cell growth, differentiation, and transcriptional regulation. However, the precise mode of action of DCAF7 is unknown and its important divergence in sequence from better characterize WD40 prevent information transfer by similarity. Structural interactomic can reveal how protein–protein interactions (PPIs) occur within an organism and are essential for understanding biological functions and developing new therapeutic strategies. Using SLiMAn2, AlphaFold2/3 and PSSMsearch, we identified a conserved α-helical short linear motif (SLiM) in several well known DCAF7 partners that binds to the top surface of its β-propeller. This motif was subsequently used to generate a regular expression, to identify potential new direct binders across the DCAF7 meta-interactome and the human proteome. Domain-domain interactions were also predicted for some other partners. Finally, modeling of oligomeric complexes with such new hits reveals the structural basis of DCAF7 scaffolding, with links to neurodevelopmental disorders such as autism.
Related
- Multivalent Scaffolding by XIST E-Repeats Tunes RNA Binding Protein Cooperativity and Lowers the Phase Separation Threshold
- Design of Tissue-Selective PROTACs Through Recruiting E3 Ligase Scaffolding Protein MAGEA11
- Static Recovery Is Not Dynamic Stability: Dynamics-Aware Benchmarking of Protein Motif Scaffolding
- Immunomodulatory Effects of Galleria mellonella and Alphitobius diaperinus Protein Digestates Generated Using a Modified INFOGEST Protocol - In Vitro and In Silico Evidence.
- Evaluation of the immunogenic properties of a chimeric protein against West Nile virus: in-silico analysis and assessment in mouse
BibTeX
@misc{mezghrani2026silico,
title = {{In Silico Structure-Based Interactomic Analysis of the Scaffolding Protein DCAF7}},
author = {Alexandre Mezghrani and Victor Reys and Gilles Labesse},
howpublished = {BioRxiv},
year = {2026},
month = may,
doi = {10.64898/2026.05.13.724911},
url = {https://hal.science/hal-05843762v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - In Silico Structure-Based Interactomic Analysis of the Scaffolding Protein DCAF7
AU - Alexandre Mezghrani
AU - Victor Reys
AU - Gilles Labesse
PY - 2026
DA - 2026/05/15
PB - BioRxiv
DO - 10.64898/2026.05.13.724911
UR - https://hal.science/hal-05843762v1
AB - WD40 domains share a widespread β-propeller fold, and often act as versatile scaffold proteins. Despite their central role in organizing dynamic cellular complexes, the molecular and structural mechanisms of many WD40 proteins remain poorly understood. Among them, DCAF7, an ubiquitously expressed and essential gene in human, also encodes a highly conserved WD40 protein in eukaryotic organisms. It is known to interact with multiple and functionnally diverse partners to coordinates cellular activity of several protein kinases as well as transcriptional regulators, thereby modulating key cellular processes such as cell growth, differentiation, and transcriptional regulation. However, the precise mode of action of DCAF7 is unknown and its important divergence in sequence from better characterize WD40 prevent information transfer by similarity. Structural interactomic can reveal how protein–protein interactions (PPIs) occur within an organism and are essential for understanding biological functions and developing new therapeutic strategies. Using SLiMAn2, AlphaFold2/3 and PSSMsearch, we identified a conserved α-helical short linear motif (SLiM) in several well known DCAF7 partners that binds to the top surface of its β-propeller. This motif was subsequently used to generate a regular expression, to identify potential new direct binders across the DCAF7 meta-interactome and the human proteome. Domain-domain interactions were also predicted for some other partners. Finally, modeling of oligomeric complexes with such new hits reveals the structural basis of DCAF7 scaffolding, with links to neurodevelopmental disorders such as autism.
SN - 2692-8205
ER -