human il 7rα ectodomain  (R&D Systems)

Journal: bioRxiv

Article Title: Phage Display-Derived Cyclic Peptides Target TREM2 and Modulate Microglial Responses under Amyloid Stress

doi: 10.64898/2026.04.22.720287

Figure Lengend Snippet: (A) Schematic of the phage display workflow. The extracellular domain of TREM2 was used as the target for selection from a cysteine-constrained cyclic peptide M13 phage library. Four rounds of biopanning, including binding, washing, elution, and amplification, were performed to enrich TREM2-binding clones. (B) Top enriched peptide sequences identified from rounds 2-4. Filled circles indicate detection of a given sequence in the corresponding round, while open circles indicate absence. All sequences conform to a cysteine-constrained cyclic peptide scaffold. (C) Phage ELISA validation of selected peptides. Binding signals are presented as the ratio of signal obtained in TREM2-coated wells relative to control wells lacking protein (E/C). Values above 1 indicate preferential binding to TREM2. Data are shown as mean ± SEM (n=3).

Article Snippet: A 10 μM solution of the His-tagged TREM2 ectodomain (SinoBiological, 11084-H08H) was labeled using the RED-maleimide 2 nd generation dye (NanoTemper, MO-L014) according to the manufacturer’s protocol (labeling buffer: 10 mM HEPES pH 7.4, 150 mM NaCl, 0.5 mM TCEP, 0.05% Tween-20), resulting in a 0.90 μM stock of labeled protein (“TREM2-maleimide-dye”) in storage buffer (HBSP: 10 mM HEPES pH 7.4, 150 mM NaCl, 0.05% Tween-20) with a final degree of labeling (DOL) of 0.596.

Techniques: Selection, Binding Assay, Amplification, Clone Assay, Sequencing, Enzyme-linked Immunosorbent Assay, Biomarker Discovery, Control

Journal: bioRxiv

Article Title: Phage Display-Derived Cyclic Peptides Target TREM2 and Modulate Microglial Responses under Amyloid Stress

doi: 10.64898/2026.04.22.720287

Figure Lengend Snippet:

Article Snippet: A 10 μM solution of the His-tagged TREM2 ectodomain (SinoBiological, 11084-H08H) was labeled using the RED-maleimide 2 nd generation dye (NanoTemper, MO-L014) according to the manufacturer’s protocol (labeling buffer: 10 mM HEPES pH 7.4, 150 mM NaCl, 0.5 mM TCEP, 0.05% Tween-20), resulting in a 0.90 μM stock of labeled protein (“TREM2-maleimide-dye”) in storage buffer (HBSP: 10 mM HEPES pH 7.4, 150 mM NaCl, 0.05% Tween-20) with a final degree of labeling (DOL) of 0.596.

Techniques: Binding Assay

Journal: bioRxiv

Article Title: Phage Display-Derived Cyclic Peptides Target TREM2 and Modulate Microglial Responses under Amyloid Stress

doi: 10.64898/2026.04.22.720287

Figure Lengend Snippet: (A) IL-1β secretion in human iPSC-derived microglia following Aβ 1-42 oligomer challenge in the presence of TREM2-6 or TREM2-12 (5, 10, and 25 µM). VG-3927 (5 μM) was used as a positive control. Data are normalized to the Aβ-treated vehicle control and expressed as percent change. (B) Loss of peptide-mediated suppression of IL-1β secretion in TREM2 knockout (KO) microglia confirms TREM2-dependent activity. (C) Modulation of secreted ApoE levels in human microglia following Aβ exposure and peptide treatment (25 µM). ApoE levels are normalized to vehicle-treated controls. Data are presented as mean ± SD (n = 5). Statistical significance was determined by one-way or two-way ANOVA with Dunnett’s post hoc test. ns , not significant; p < 0.05 (*), p < 0.01 (**), p < 0.001 (***), and p < 0.0001 (****) relative to vehicle treatment.

Article Snippet: A 10 μM solution of the His-tagged TREM2 ectodomain (SinoBiological, 11084-H08H) was labeled using the RED-maleimide 2 nd generation dye (NanoTemper, MO-L014) according to the manufacturer’s protocol (labeling buffer: 10 mM HEPES pH 7.4, 150 mM NaCl, 0.5 mM TCEP, 0.05% Tween-20), resulting in a 0.90 μM stock of labeled protein (“TREM2-maleimide-dye”) in storage buffer (HBSP: 10 mM HEPES pH 7.4, 150 mM NaCl, 0.05% Tween-20) with a final degree of labeling (DOL) of 0.596.

Techniques: Derivative Assay, Positive Control, Control, Knock-Out, Activity Assay

Journal: bioRxiv

Article Title: Phage Display-Derived Cyclic Peptides Target TREM2 and Modulate Microglial Responses under Amyloid Stress

doi: 10.64898/2026.04.22.720287

Figure Lengend Snippet: Quantification of PSD95 levels in human iPSC-derived neuron-microglia co-cultures following Aβ 1-42 oligomer exposure and treatment with TREM2-6 or TREM2-12 (5, 10, and 25 µM). VG-3927 (5 μM) was used as a positive control. PSD95 levels are expressed as percent rescue relative to Aβ-treated vehicle controls. Data are presented as mean ± SD (n = 5). Statistical significance was assessed by one-way ANOVA with Dunnett’s post hoc test. p < 0.05 (*), p < 0.01 (**), p < 0.001 (***), and p < 0.0001 (****) relative to vehicle treatment.

Article Snippet: A 10 μM solution of the His-tagged TREM2 ectodomain (SinoBiological, 11084-H08H) was labeled using the RED-maleimide 2 nd generation dye (NanoTemper, MO-L014) according to the manufacturer’s protocol (labeling buffer: 10 mM HEPES pH 7.4, 150 mM NaCl, 0.5 mM TCEP, 0.05% Tween-20), resulting in a 0.90 μM stock of labeled protein (“TREM2-maleimide-dye”) in storage buffer (HBSP: 10 mM HEPES pH 7.4, 150 mM NaCl, 0.05% Tween-20) with a final degree of labeling (DOL) of 0.596.

Techniques: Derivative Assay, Positive Control

Journal: bioRxiv

Article Title: Phage Display-Derived Cyclic Peptides Target TREM2 and Modulate Microglial Responses under Amyloid Stress

doi: 10.64898/2026.04.22.720287

Figure Lengend Snippet: (A) Time-dependent root-mean-square deviation (RMSD) of the TREM2 receptor in the free form (cyan line) and in complex with T6 (purple line) and T12 (yellow line) over a 100 ns MD simulation. (B) RMSD of the T6 and T12 over a 100-ns MD simulation.

Article Snippet: A 10 μM solution of the His-tagged TREM2 ectodomain (SinoBiological, 11084-H08H) was labeled using the RED-maleimide 2 nd generation dye (NanoTemper, MO-L014) according to the manufacturer’s protocol (labeling buffer: 10 mM HEPES pH 7.4, 150 mM NaCl, 0.5 mM TCEP, 0.05% Tween-20), resulting in a 0.90 μM stock of labeled protein (“TREM2-maleimide-dye”) in storage buffer (HBSP: 10 mM HEPES pH 7.4, 150 mM NaCl, 0.05% Tween-20) with a final degree of labeling (DOL) of 0.596.

Techniques:

Journal: bioRxiv

Article Title: Phage Display-Derived Cyclic Peptides Target TREM2 and Modulate Microglial Responses under Amyloid Stress

doi: 10.64898/2026.04.22.720287

Figure Lengend Snippet: B) Structural snapshot clustered from the late stage of the MD simulation of T12 (A) and T6 (B) complexed with TREM2. The receptor is shown in grey cartoon, T12 is shown in blue sticks, and T6 is shown in orange sticks. (C and D) Views of the binding interface between T12 (C) / T6 (D) and TREM2 with the key interacting residues on both sides and yellow dashed lines that demonstrate stable hydrogen bonds and salt bridges.

Article Snippet: A 10 μM solution of the His-tagged TREM2 ectodomain (SinoBiological, 11084-H08H) was labeled using the RED-maleimide 2 nd generation dye (NanoTemper, MO-L014) according to the manufacturer’s protocol (labeling buffer: 10 mM HEPES pH 7.4, 150 mM NaCl, 0.5 mM TCEP, 0.05% Tween-20), resulting in a 0.90 μM stock of labeled protein (“TREM2-maleimide-dye”) in storage buffer (HBSP: 10 mM HEPES pH 7.4, 150 mM NaCl, 0.05% Tween-20) with a final degree of labeling (DOL) of 0.596.

Techniques: Binding Assay

Journal: eBioMedicine

Article Title: Nucleoprotein and glycoprotein based serological assays for detection of Marburg virus infections

doi: 10.1016/j.ebiom.2026.106244

Figure Lengend Snippet: Schematic representation of the MARV nucleoprotein C-terminal tail (NPct) MR assay principle. (A) The MARV nucleoprotein structure showing the N-terminal arm, NP core, disordered linker, and C-terminal tail region. (B) The Nanoluc can be split into inactive LgBit and SmBit fragments. Biosensor design featuring SmBit-NPct and LgBit-NPct fusion proteins. In the absence of anti-MARV NPct antibodies, the biosensor remains inactive with separated NanoLuc fragments. (C) Upon addition of serum containing anti-NPct antibodies, bivalent antibodies bind to both SmBit-NPct and LgBit-NPct, bringing the fragments into proximity to reconstitute active luciferase and generate luminescent signal.

Article Snippet: The MARV GP ectodomain from Angola 2005 strain (GenBank: DQ447660.1 , residues 1–637) with a C-terminal 8X His-tag and AviTag was codon-optimised for human cell expression, synthesised, and cloned into pEEV-Puro vector by Twist Bioscience.

Techniques: Luciferase

Journal: eBioMedicine

Article Title: Nucleoprotein and glycoprotein based serological assays for detection of Marburg virus infections

doi: 10.1016/j.ebiom.2026.106244

Figure Lengend Snippet: MARV NPct MR assay workflow. The assay protocol involves three simple steps: (1) addition of serum sample and biosensor components with 20-min incubation, (2) addition of NanoLuc substrate with 10-min incubation, and (3) luminescence measurement.

Article Snippet: The MARV GP ectodomain from Angola 2005 strain (GenBank: DQ447660.1 , residues 1–637) with a C-terminal 8X His-tag and AviTag was codon-optimised for human cell expression, synthesised, and cloned into pEEV-Puro vector by Twist Bioscience.

Techniques: Incubation

Journal: eBioMedicine

Article Title: Nucleoprotein and glycoprotein based serological assays for detection of Marburg virus infections

doi: 10.1016/j.ebiom.2026.106244

Figure Lengend Snippet: Performance assessment of the MARV NPct MR assay using historical MVD and EVD recovered patient samples. (A) Individual raw relative luminescence units (RLU) versus (B) individual normalised RLU from RT-PCR confirmed MVD cases from previous outbreaks (South Africa 1975, Kenya 1980, Uganda 2012, n = 5) are compared to negative control samples from the USA (n = 168) and Ebola virus disease recovered patients (n = 8). The assay demonstrated approximately 129-fold higher signal in MVD cases compared to negative controls. Data are presented as mean ± SD.

Article Snippet: The MARV GP ectodomain from Angola 2005 strain (GenBank: DQ447660.1 , residues 1–637) with a C-terminal 8X His-tag and AviTag was codon-optimised for human cell expression, synthesised, and cloned into pEEV-Puro vector by Twist Bioscience.

Techniques: Reverse Transcription Polymerase Chain Reaction, Negative Control, Virus

Journal: eBioMedicine

Article Title: Nucleoprotein and glycoprotein based serological assays for detection of Marburg virus infections

doi: 10.1016/j.ebiom.2026.106244

Figure Lengend Snippet: MARV NPct MR assay performance in the Rwanda validation cohort. (A) ROC curve showing discrimination between RT-PCR confirmed MVD cases (n = 36) and control samples including low-risk contacts (n = 46) and pre-outbreak samples (n = 243). Area under the curve (AUC) = 0.996 [95% CI, 0.990–1.000]. (B) Distribution of normalised individual RLU values for negative controls (black) and MVD cases (red), with the optimal cut-off threshold of 24.22 indicated by the dashed line. Statistical significance was determined using the Kruskal–Wallis test (p < 0.0001). Data are presented as mean ± SD.

Article Snippet: The MARV GP ectodomain from Angola 2005 strain (GenBank: DQ447660.1 , residues 1–637) with a C-terminal 8X His-tag and AviTag was codon-optimised for human cell expression, synthesised, and cloned into pEEV-Puro vector by Twist Bioscience.

Techniques: Biomarker Discovery, Reverse Transcription Polymerase Chain Reaction, Control

Journal: eBioMedicine

Article Title: Nucleoprotein and glycoprotein based serological assays for detection of Marburg virus infections

doi: 10.1016/j.ebiom.2026.106244

Figure Lengend Snippet: Species-agnostic performance of the MARV NPct MR assay in Rousettus aegyptiacus bats. (A) ROC curve analysis demonstrating perfect discrimination (AUC = 1.0) between experimentally MARV-infected Rousettus aegyptiacus bats (n = 20) and uninfected controls (n = 5). (B) Distribution of individual normalised RLU values for uninfected control bats (black) and MARV-infected bats (red), with the optimal cut-off threshold of 2.2 achieving 100% sensitivity and 100% specificity. Statistical significance was determined using the two-tailed Mann–Whitney U test (p < 0.0001). Data are presented as mean ± SD.

Article Snippet: The MARV GP ectodomain from Angola 2005 strain (GenBank: DQ447660.1 , residues 1–637) with a C-terminal 8X His-tag and AviTag was codon-optimised for human cell expression, synthesised, and cloned into pEEV-Puro vector by Twist Bioscience.

Techniques: Infection, Control, Two Tailed Test, MANN-WHITNEY

Journal: eBioMedicine

Article Title: Nucleoprotein and glycoprotein based serological assays for detection of Marburg virus infections

doi: 10.1016/j.ebiom.2026.106244

Figure Lengend Snippet: MARV GP ELISA performance in the Rwanda validation cohort. (A) ROC curve analysis for the anti-GP ELISA using corrected absorbance values at 1:100 dilution. AUC = 0.973 [95% CI, 0.922–1.000], with cut-off of 0.3 achieving 94.4% sensitivity [95% CI, 81.9%–99.0%] and 100% specificity [95% CI, 92.3%–100%]. (B) Distribution of individual corrected optical density values at dilution 1:100 for low-risk contacts (n = 46, black) and RT-PCR confirmed MVD cases (n = 36, red), with the assay cut-off threshold indicated by the dashed line. Statistical significance was determined using the two-tailed Mann–Whitney U test (p < 0.0001). Data are presented as mean ± SD.

Article Snippet: The MARV GP ectodomain from Angola 2005 strain (GenBank: DQ447660.1 , residues 1–637) with a C-terminal 8X His-tag and AviTag was codon-optimised for human cell expression, synthesised, and cloned into pEEV-Puro vector by Twist Bioscience.

Techniques: Enzyme-linked Immunosorbent Assay, Biomarker Discovery, Reverse Transcription Polymerase Chain Reaction, Two Tailed Test, MANN-WHITNEY

Journal: eBioMedicine

Article Title: Nucleoprotein and glycoprotein based serological assays for detection of Marburg virus infections

doi: 10.1016/j.ebiom.2026.106244

Figure Lengend Snippet: Concordance between the MARV NPct MR assay and MARV glycoprotein GP ELISA. Normalised relative luminescence units (RLU) from the NPct MR assay are plotted against corrected optical density (OD) values at 1:100 dilution from the GP ELISA for (A) low-risk contacts (n = 46, black symbols) and (B) RT-PCR-confirmed MVD cases (n = 36, red symbols). Horizontal and vertical dashed lines indicate the respective assay cutoff thresholds (NPct MR: normalised RLU > 24.22; GP ELISA: OD > 0.3). All samples showed concordant results, with perfect agreement (82/82) in diagnostic classification between assays. Correlation between the assays was statistically significant (Spearman r = 0.6960; 95% CI, 0.5598–0.7956; p < 0.0001).

Article Snippet: The MARV GP ectodomain from Angola 2005 strain (GenBank: DQ447660.1 , residues 1–637) with a C-terminal 8X His-tag and AviTag was codon-optimised for human cell expression, synthesised, and cloned into pEEV-Puro vector by Twist Bioscience.

Techniques: Enzyme-linked Immunosorbent Assay, Reverse Transcription Polymerase Chain Reaction, Diagnostic Assay

Journal: mAbs

Article Title: Targeting IL-7Rα with PNU-159682 antibody–drug conjugates in acute lymphoblastic leukemia: translational implications

doi: 10.1080/19420862.2026.2663639

Figure Lengend Snippet: Generation and characterization of IL-7Rα-targeting antibodies. (a) Schematic workflow of IL-7Rα-specific monoclonal antibodies (mAbs) generation: immunization of IL-7Rα-knockout mice with recombinant human IL-7Rα extracellular domain, hybridoma fusion, and screening/expansion, followed by conversion to human–mouse chimeric IgG. (b) Flow cytometry histograms showing the binding capabilities of in-house clones 577, 2D5, 165, and 24 to IL-7Rα-positive cells compared with a commercial anti-IL-7Rα mAb; secondary-only and unstained controls are included. (c) Competitive binding (epitope binning) assessment between different in-house antibody pairs using flow cytometry. Cells were pre-blocked with an unlabeled antibody and stained with a fluorophore-labelled competitor. The binding ratios were normalized to the non-pre-blocked condition. (d) Surface plasmon resonance analysis of antibody binding to recombinant IL-7Rα.

Article Snippet: His-tagged recombinant human IL-7Rα ectodomain (R&D Systems, Minneapolis, MN, USA, Cat. No. 10758-IR) was captured on the active flow cell to approximately 50 response units (RU).

Techniques: Bioprocessing, Knock-Out, Recombinant, Flow Cytometry, Binding Assay, Clone Assay, Staining, SPR Assay

Journal: mAbs

Article Title: Targeting IL-7Rα with PNU-159682 antibody–drug conjugates in acute lymphoblastic leukemia: translational implications

doi: 10.1080/19420862.2026.2663639

Figure Lengend Snippet: Generation and cytotoxicity assessment of IL-7Rα-targeting ADCs. (a) Internalization kinetics of four IL-7Rα-targeting monoclonal antibodies in IL-7Rα-positive REH cells. Surface-bound antibody levels of the four antibodies at 0, 15, 60, and 240 minutes were determined by flow cytometry and normalized to the signal at minute 0. (b) Schematic representation of the conjugation process for generating IL-7Rα-targeting ADCs. Antibodies were partially reduced with 20 mM 2-mercaptoethylamine (2-MEA) for 0.5 hours at 37°C, followed by conjugation with 10 mM mc–vc–PAB–MMAE for 16 hours at 4°C, yielding an average drug-to-antibody ratio of 3–4. (c) Quantification of IL-7Rα expression (molecules per cell) in three different leukemia cell lines, CCRF-CEM (low), NALM6 (medium), and REH (high), using flow cytometry. (d) Cytotoxicity of free MMAE, isotype control IgG–MMAE, and four IL-7Rα-targeting ADCs in CCRF-CEM, NALM6, and REH cells. Cell viability was assessed using the WST-8 assay 72 hours after each treatment. Data are presented as mean ± SEM; n = 6 technical replicates from a single experiment.

Article Snippet: His-tagged recombinant human IL-7Rα ectodomain (R&D Systems, Minneapolis, MN, USA, Cat. No. 10758-IR) was captured on the active flow cell to approximately 50 response units (RU).

Techniques: Bioprocessing, Flow Cytometry, Conjugation Assay, Expressing, Control

Journal: mAbs

Article Title: Targeting IL-7Rα with PNU-159682 antibody–drug conjugates in acute lymphoblastic leukemia: translational implications

doi: 10.1080/19420862.2026.2663639

Figure Lengend Snippet: In vivo efficacy and biodistribution of IL-7Rα-targeting agents. (a) Schematic representation of the subcutaneous tumor model and treatment schedule with four IL-7Rα-targeting ADCs. (b) Tumor volumes over time for each treatment group. (c) Relative body weight changes during treatment. PBS, phosphate-buffered saline. Lines show mean ± SEM, n = 6–9 per group. (d) Serial in vivo fluorescence imaging of fluorophore-labelled parent anti-IL-7Rα mAbs and an isotype antibody control in a separate tracer-dose cohort (representative animals). (e) Quantification of tumor region-of-interest (ROI) fluorescence; each animal was normalized to its own 5-min post-injection value. NC, negative control. Data are presented as mean ± SEM; n = 3–5 per group. (f) Relative performance of the four anti-IL-7Rα mAbs (577, 2D5, 165, and 24) was compared across five parameters. Binding activity, SPR-derived apparent binding affinity, internalization, and pIC 50 (-log10 IC 50 [M]) and in vivo efficacy were evaluated using the respective ADCs. Ratings were assigned based on the experimental data shown in , using a semi-quantitative scale from “+” (lowest) to “++++” (highest). The scale reflects the relative ranking within each parameter and does not represent absolute quantitative values.

Article Snippet: His-tagged recombinant human IL-7Rα ectodomain (R&D Systems, Minneapolis, MN, USA, Cat. No. 10758-IR) was captured on the active flow cell to approximately 50 response units (RU).

Techniques: In Vivo, Saline, Fluorescence, Imaging, Control, Injection, Negative Control, Binding Assay, Activity Assay, Derivative Assay

Journal: mAbs

Article Title: Targeting IL-7Rα with PNU-159682 antibody–drug conjugates in acute lymphoblastic leukemia: translational implications

doi: 10.1080/19420862.2026.2663639

Figure Lengend Snippet: Enhanced anti-tumor activity of IL-7Rα-targeting ADCs with novel payload PNU-159682. (a) Schematic representation of the conjugation process for generating PNU-159682-linked ADCs. Antibodies were partially reduced with 20 mM 2-mercaptoethylamine (2-MEA) for 0.5 hours at 37 °C, followed by conjugation with 10 mM Mal–PEG4–VC–PAB–DMEA–PNU-159682 for 16 hours at 4 °C, yielding a drug-to-antibody ratio of 3–4. (b) In vitro cytotoxicity of 577-PNU, 577-MMAE, isotype control IgG–PNU, and free PNU-159682 in NALM6 cells. Cell viability was measured using the WST-8 assay 72 hours after treatment. Data are shown as mean ± SEM. (c) Comparison of IC 50 values between 577-MMAE and 577-PNU in NALM6 cells, calculated from nine independent experiments performed on separate days; IC 50 values analyzed after log10 transformation; paired t-test (two-tailed), p < 0.0001; geometric mean ratio (MMAE/PNU) = 85.3 (95% CI 57.7–126.0). (d) In vivo anti-tumor efficacy of each treatment in NALM6 xenografts (subcutaneous model). Mice were treated with a single dose of 577-MMAE (10 mg/kg; n = 4), 577-PNU (0.5 mg/kg; n = 5), isotype control IgG–PNU (0.5 mg/kg; n = 4), free PNU-159682 (17 µg/kg, the dose of PNU equal to 0.5 mg/kg 577-PNU; n = 3), or phosphate-buffered saline (PBS) vehicle ( n = 5). Tumor volumes were measured twice weekly. (e) Complete response (CR) rate on day 28 following treatment with 577-MMAE (10 mg/kg; n = 4) or 577-PNU (0.5 mg/kg; n = 5). Two-sided Fisher’s exact test comparing groups: p = 0.0476. (f) Relative body weight change (%) during treatment. Data are presented as mean ± SEM; n = 3–5 per group. * p < 0.05; **** p < 0.0001.

Article Snippet: His-tagged recombinant human IL-7Rα ectodomain (R&D Systems, Minneapolis, MN, USA, Cat. No. 10758-IR) was captured on the active flow cell to approximately 50 response units (RU).

Techniques: Activity Assay, Conjugation Assay, In Vitro, Control, Comparison, Transformation Assay, Two Tailed Test, In Vivo, Saline

Journal: bioRxiv

Article Title: XL-MS and De Novo Protein Design Identified a Common Motif for TREM2 Binding

doi: 10.64898/2026.04.23.720433

Figure Lengend Snippet: (a) SDS-PAGE analysis showing successful cross-linking of the heterodimeric TREM2 ECD /Trx-ApoE3 complex. (b) Representative high-quality MS/MS spectra of inter-protein cross-linked peptides. (c) Bar representation showing intra-protein XLs, inter-protein XLs, and inter-protein self-links. Figure was created using xiNET . ApoE3: light blue (N-terminal region, residues 1-167), light yellow (hinge region, residues 168-205), and pink (C-terminal region, residues 206-299).

Article Snippet: 20 μM Trx-ApoE3 (Sino Biological 10817-H30E) and 20 μM TREM2 ectodomain were incubated for 1 h at 4°C.

Techniques: SDS Page, Tandem Mass Spectroscopy

Journal: bioRxiv

Article Title: XL-MS and De Novo Protein Design Identified a Common Motif for TREM2 Binding

doi: 10.64898/2026.04.23.720433

Figure Lengend Snippet: (a) Mapping intra-ApoE3 cross-links onto the NMR structure (pdb 2L7B). Red line: incompatible XLs with Cβ-Cβ solvent accessible surface distance (SASD) > 35 Å. Blue line: compatible XLs. (b) Filtering the structure ensemble of ApoE3 (Protein Ensemble Database PED07094) by intra-ApoE3 XLs yielded Model 49 with the highest structural compatibility. (c) The best-scoring model of TREM2/ApoE3 complex generated using Haddock. (d) Zoom-in view of the binding interface. ApoE3: light blue (N-terminal region, residues 1-167), light yellow (hinge region, residues 168-205), and pink (C-terminal region, residues 206-299). TREM2 ECD : CDR1(residue 40-42), CDR2(residue 69-72), and CDR3 (residue 88-91).

Article Snippet: 20 μM Trx-ApoE3 (Sino Biological 10817-H30E) and 20 μM TREM2 ectodomain were incubated for 1 h at 4°C.

Techniques: Solvent, Generated, Binding Assay, Residue

Journal: bioRxiv

Article Title: XL-MS and De Novo Protein Design Identified a Common Motif for TREM2 Binding

doi: 10.64898/2026.04.23.720433

Figure Lengend Snippet: (a-m) Design models of mini-proteins in complex with TREM2 ECD (left) and binding affinity determined by microscale thermophoresis (right). Numbers in brackets represent the 68.3% confidence interval calculated by “error-surface projection” .

Article Snippet: 20 μM Trx-ApoE3 (Sino Biological 10817-H30E) and 20 μM TREM2 ectodomain were incubated for 1 h at 4°C.

Techniques: Binding Assay, Microscale Thermophoresis