ArticleProtein science : a publication of the Protein Society2016
Comparison of the peptide binding preferences of three closely related TRAF paralogs: TRAF2, TRAF3, and TRAF5.
Article in Protein science : a publication of the Protein Society, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- CD40 Agonism in Pancreatic Ductal Adenocarcinoma: Expression, Biology, and Therapeutic Targeting.Cancers · 2026Review
- The effect of CD40 agonist antibody therapy on the pancreatic cancer microenvironment.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Defining short linear motif binding determinants by phage display-based deep mutational scanning.Protein science : a publication of the Protein Society · 2025Article
- Elaboration of the Homer1 recognition landscape reveals incomplete divergence of paralogous EVH1 domains.Protein science : a publication of the Protein Society · 2024Article
- Elaboration of the Homer1 Recognition Landscape Reveals Incomplete Divergence of Paralogous EVH1 Domains.bioRxiv : the preprint server for biology · 2024Article
- The Roles of TRAF3 in Immune Responses.Disease markers · 2023Review
- Molecular determinants of TRAF6 binding specificity suggest that native interaction partners are not optimized for affinity.Protein science : a publication of the Protein Society · 2022Article
- Native proline-rich motifs exploit sequence context to target actin-remodeling Ena/VASP protein ENAH.eLife · 2022Article
- Comparison of Target Recognition by TRAF1 and TRAF2.International journal of molecular sciences · 2020Article
- Roles of TRAFs in Ischemia-Reperfusion Injury.Frontiers in cell and developmental biology · 2020Review
- AncientJournal of immunology (Baltimore, Md. : 1950) · 2019Article
- MaveDB: an open-source platform to distribute and interpret data from multiplexed assays of variant effect.Genome biology · 2019Article
- TRAF molecules in inflammation and inflammatory diseases.Current pharmacology reports · 2018Article
- CD137 (4-1BB) Signalosome: Complexity Is a Matter of TRAFs.Frontiers in immunology · 2018Review
- Structure of TRAF Family: Current Understanding of Receptor Recognition.Frontiers in immunology · 2018Review
- Rapid Optimization of Mcl-1 Inhibitors using Stapled Peptide Libraries Including Non-Natural Side Chains.ACS chemical biology · 2016Article
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2 authors at 1 institution in 1 country.
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Abstract
Tumor necrosis factor receptor-associated factors (TRAFs) constitute a family of adapter proteins that act in numerous signaling pathways important in human biology and disease. The MATH domain of TRAF proteins binds peptides found in the cytoplasmic domains of signaling receptors, thereby connecting extracellular signals to downstream effectors. Beyond several very general motifs, the peptide binding preferences of TRAFs have not been extensively characterized, and differences between the binding preferences of TRAF paralogs are poorly understood. Here we report a screening system that we established to explore TRAF peptide-binding specificity using deep mutational scanning of TRAF-peptide ligands. We displayed single- and double-mutant peptide libraries based on the TRAF-binding sites of CD40 or TANK on the surface of Escherichia coli and screened them for binding to TRAF2, TRAF3, and TRAF5. Enrichment analysis of the library sequencing results showed differences in the permitted substitution patterns in the TANK versus CD40 backgrounds. The three TRAF proteins also demonstrated different preferences for binding to members of the CD40 library, and three peptides from that library that were analyzed individually showed striking differences in affinity for the three TRAFs. These results illustrate a previously unappreciated level of binding specificity between these close paralogs and demonstrate that established motifs are overly simplistic. The results from this work begin to outline differences between TRAF family members, and the experimental approach established herein will enable future efforts to investigate and redesign TRAF peptide-binding specificity.
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