Work

Structural insights into bromodomain-containing complexes from Trypanosoma cruzi revealed by proximity labeling and stoichiometric space exploration

Year: 2026

Type: article

Abstract: Trypanosoma cruzi , the etiological agent of Chagas disease, remains a major health concern due to the limited efficacy and toxicity of current treatments. Bromodomain factors (BDFs), which recognize acetylated lysine residues, are key components of epigenetic regulatory machinery and represent promising therapeutic targets. Despite their importance, structural organization of bromodomain-containing complexes in trypanosomatids is poorly understood. In this study, we combined experimental and computational approaches to investigate the composition and stoichiometry of BDF-containing complexes in T. cruzi . Using TurboID-based proximity labeling, we mapped interaction networks for five BDFs (BDF3, BDF4, BDF5, BDF6 and BDF8) and identified two major complexes, CRKT and NuA4. To further resolve their architecture, we applied structure prediction methods that explore multiple stoichiometric configurations. Our analyses indicate that CRKT is organized into three modules with distinct interaction dynamics, whereas NuA4 comprises two modules. The CRKT core module displays a symmetric arrangement containing two copies of BDF3, BDF5, and BDF8. Its catalytic module contains three subunits including HAT2, while the BET module contains BDF4 and BDF1. In NuA4, the catalytic module resembles the yeast piccolo-NuA4 complex and includes HAT1, with the TINTIN module associating via BDF6. These findings provide structural insights into epigenetic complexes in trypanosomatids and support their potential as drug targets.

Source: Scientific Reports

DOI: 10.1038/s41598-026-78581-4

Authors: Elvio Rodríguez Araya, Gonzalo Martínez Peralta, Victoria Alonso, Esteban Serra

Institutions: Consejo Nacional de Investigaciones Científicas y Técnicas, National University of Rosario, Instituto de Biología Molecular y Celular de Rosario

Language: English

Topic: Trypanosoma species research and implications

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

Open Access status: gold

Estimated APC paid: $2,690

Funders: Universidad Nacional de Rosario, Consejo Nacional de Investigaciones Científicas y Técnicas, Agencia Nacional de Promoción Científica y Tecnológica