Ask about this productRelated genes to: BRD3 antibody
- Gene:
- BRD3 NIH gene
- Name:
- bromodomain containing 3
- Previous symbol:
- -
- Synonyms:
- RING3L, ORFX, KIAA0043
- Chromosome:
- 9q34.2
- Locus Type:
- gene with protein product
- Date approved:
- 2000-07-25
- Date modifiied:
- 2016-10-05
Related products to: BRD3 antibody
Related articles to: BRD3 antibody
- We previously showed that AlphaFold2 can be used to screen for peptide-binding epitopes targeting the extraterminal (ET) domain of Bromodomain and Extraterminal (BET) proteins from candidate protein partners identified in pull-down experiments. However, such approaches require large numbers of AlphaFold2 calculations, making exhaustive screening impractical for larger datasets, such as viral proteomes that may target the ET domain. In many cases, identifying a substantial fraction of binders-even without exhaustive coverage-would already provide valuable biological insight into these interaction networks. Here, we show that an active learning strategy based on Thompson sampling (TS) can efficiently explore peptide sequence space. Using a library derived from BRD3 pull-down experiments, TS recovers 50% of all binders using 15% of the queries required by exhaustive sampling (3.3 times improvement over random sampling). Moreover, TS consistently identifies experimentally known binding epitopes with substantially fewer queries. Because the approach relies only on binary labels, it is readily transferable to other protein-peptide systems where AF-based binding classification is applicable, as well as to peptide-property predictors for properties such as solubility or aggregation propensity. - Source: PubMed
Publication date: 2026/04/18
Gaza JokentSantos Jherome Brylle WoodySingh BhumikaMiranda-Quintana Ramón AlainPerez Alberto - The engineered formation of ternary complexes, in which two proteins are bridged by small molecules such as PROTACs or molecular glues, is a prerequisite for the targeted enzymatic degradation of pathogenic proteins; however, the combined analysis of these ternary interactions during the drug discovery process remains challenging. Here, we introduce a proximity binding assay for the simultaneous measurement of binary and ternary interaction kinetics on a biosensor surface. Target proteins and the substrate binding subunit of ubiquitin E3 ligase are tethered to mobile swivel arms of a Y-shaped DNA scaffold. The Y-structure induces spatial proximity between the proteins and presents them to PROTAC analytes flown across the sensor. PROTAC-induced ternary complex formation is measured by fluorescence energy transfer (FRET), while binary interactions are detected by fluorescence quenching. The assay is applied to cereblon (CRBN) and von Hippel-Lindau (VHL) as E3 ligase substrate receptors, a range of compounds including AT1, MZ1, dBETs, and ARV-825 as PROTACs, and the two bromodomains of BRD2, BRD3, BRD4, and BRDT proteins as targets. Automated workflows enable the measurement of 384 real-time sensorgrams in a single run using picomole sample quantities. The insights into proximity-mediated binding kinetics can enable the development of PROTACs and molecular glues with improved properties for targeted protein degradation. - Source: PubMed
Publication date: 2026/04/21
Ponzo IreneSoldà AliceCrowe CharlotteDahl GöranJahodová TerezaHeerwig AndreasGeschwindner StefanCiulli AlessioRant Ulrich - The bromodomain and extraterminal domain (BET) family uses its conserved ET domains to recognize diverse peptide motifs, yet exhibits paralog-specific binding preferences whose structural origins remain poorly understood. Using extensive molecular dynamics (MD) simulations of BRD3-ET and BRD4-ET and experimental data for the unbound and peptide-bound states, we show that paralog selectivity arises not from large structural rearrangements but from subtle differences in the dynamics of the α2-α3 loop. Two divergent residues at positions 35 and 36 in this loop modulate the formation of flanking helices (η1 and η2), which in turn control the opening of the peptide-binding cavity and determine how each paralog accommodates distinct binding modes. These sequence-encoded dynamical differences shape the number, stability, and geometry of accessible binding modes and provide a structural rationale for paralog-specific targeting of BET proteins. - Source: PubMed
Publication date: 2026/04/15
Alvarez GuadalupeSebastian ElizabethMondal ArupRoth Monica JMontelione Gaetano TPerez Alberto - Targeted protein degradation (TPD) is a powerful strategy for controlling protein abundance. Here, we establish FBXO31 as a TPD-competent E3 ligase by exploiting its recognition of C-terminal amide-bearing degrons. Using an amidated Ala-Phe motif as a chemical recruiter, multiple small-molecule binders can be transformed into FBXO31-dependent degraders that induce the rapid and potent degradation of FKBP12, multiple kinases, and BET proteins BRD2, BRD3, and BRD4. Mechanistic studies confirm FBXO31-mediated ternary complex formation and identify key residues in FBXO31 required for recruiter engagement and target degradation. - Source: PubMed
Publication date: 2026/04/10
Zhang ChenluJin XiaokangZhou ChenJenkins M JamalRiha Isabella AZhang Xiaoyu - PROTACs offer a novel therapeutic strategy for addressing diseases driven by aberrant expression of pathogenic proteins. In this study, we identified a series of PROTAC molecules capable of degrading BRD2, BRD3, and BRD4. Structure-activity relationship analysis led to the discovery of CR10, a highly potent degrader that exhibited remarkable activity in MV4-11 cells. Mechanistic studies demonstrated that CR10 induced sustained degradation of target proteins via the ubiquitin-proteasome system. In mice models, intraperitoneal administration at 20 mg/kg achieved an exceptional bioavailability of 108.27%. Furthermore, CR10 significantly inhibited the growth of MV4-11 and A549 xenograft tumors at a dose as low as 2 mg/kg, without apparent toxicity. This semi-rigid linker-containing degrader represented a promising new mechanism-based candidate for the treatment of hematologic malignancies and lung cancer, warranting further investigation. - Source: PubMed
Publication date: 2026/02/03
Yu SuHu ShichuanWang WeilinPan ChuntaoZhang HongjiaZhou CongLiu YangLi Rui