ttk_235

[Samuel Hume @DrSamuelBHume]

Zanidatamab is a particularly good example – it's 'biparatopic', so it binds two sites in the same molecule (HER2).

This means that, as well as blocking downstream signalling, it crosslinks HER2 into clusters, with a Zanidatamab hexamer at the centre.

These clusters trigger cancer cell killing by the complement system, which the monospecific equivalent, Trastuzumab, does not do!

[Satoshi Tanaka @sato51643335]

プレスリリースを読んでみましたが、何ができるようになったのかよく分かりませんでした。タイトルの通りの技術が実現したのであれば、その結果が示されていると思いきやそうではなかったです。SDS-PAGEのパターンの高感度解析みたいな話でしょうか… https://t.co/h4yUgOCPCz

[Martin Pacesa @MartinPacesa]

Very cool design of de novo protein substrate for blue melanin production
https://t.co/ClIPuRggW7

[日本の研究.comニュース @rjp_news]

【注目プレスリリース】生きた細胞をプラットホームにした未来の医薬DNAアプタマーの創製技術「EV-SELEX法」 〜μ-オピオイド受容体を標的とする高機能DNAアプタマーの創出に成功、次世代GPCR創薬への応用に期待〜 / 順天堂大学,富山大学 https://t.co/bSpHKT9Fn9

[biohub @biohub]

Designing a protein binder used to mean years of lab experiments. ESMFold2 lets researchers run hundreds of thousands of designs computationally—then take only the most promising into the lab. We tested it across 5 targets in oncology and immunology. It worked.

Download and build: https://t.co/odrOR3U1hj

[バイオステーション(Bio-station)/ポッドキャスト @Bio_stations]

人工タンパク質による膜タンパク質の可溶化

従来水に溶けにくく解析が困難であった膜タンパク質を、デザインされた人工タンパク質「WRAP」で包み込むことで可溶化することに成功。GPCRや酵素などの水溶化に成功、元の機能も維持されるらしい
https://t.co/9p56rs8g9v

[sk @compchemm]

David Baker & Veesler labs "building viruses - Institute for Protein Design (IPD)

-Two new Nature papers - "building viruses, at University of Washington" if you believe the headlines. What they've actually done is more interesting than that.
https://t.co/EjXP70iwQX

[Ah-Ram Kim @ahramkim1128]

Clocked stepping of an artificial protein walker along a DNA track https://t.co/q6WMpQRAXX

[Tolga Bozkurt @Tolga_Bzkrt]

AlphaFold-based modelling lets us visualise these N-terminal “safety caps” and predict how they interfere with formation of the pore-forming resistosome. https://t.co/Ws1mU9fym7

[Ai Niitsu 新津 藍 @AiNiitsu212]

レビュー: Artificial metalloenzymes in complex biological environments

https://t.co/GoFtrKGOhG

[しんしあ@バイオテクコミュニティ「BioSpace」モデレーター @BioSpace9]

タンパク質の環状置換による末端位置の違いを超えて構造類似性を捉えることで、これまで見逃されやすかった進化的・構造的関係を大規模に発見できる検索モデル「CIRPIN」について紹介します！

https://t.co/mJ8ohsmZcB

#biospace

[Aggregate @AggregateOA]

Defensin-DNA Supramolecular Complexes as a New pH-Sensing Nanomaterial
https://t.co/7RsdM0mPmu

[Trends in Biotechnology @TrendsinBiotech]

Online now: Engineered Bacillus subtilis to deliver dsRNA via extracellular vesicles against the H9N2 avian influenza virus https://t.co/AmTUAYMBCz

[Ah-Ram Kim @ahramkim1128]

A High-Affinity Nanobody Recognizing mNeonGreen Enables Versatile Biochemical, Cellular, and in vivo Applications https://t.co/3ZxLUGuDkg

[Biology+AI Daily @BiologyAIDaily]

A Generalizable Interface-Seeded Framework for De Novo Design of Functional Oligomers

1. The paper introduces an “interface-seeded” generative design strategy: instead of docking existing protein building blocks into a target symmetry, it uses a previously validated protein–protein interface (PPI) as the seed and generates new symmetry-compatible protomers around it.

2. Key implementation detail: a new symmetric motif-scaffolding module in RFdiffusion that preserves the interface motifs while sampling seed orientations and radial placements, then “drags” the motif radially during denoising to bias toward compact, well-packed cyclic oligomers.

3. This directly addresses a practical bottleneck in symmetric assembly design: dock-and-design success is often limited by geometric incompatibility between chosen protomers and target symmetries (C3/C4/C5), producing strong biases and low hit rates.

4. Benchmarking with LHD heterodimer seeds (LHD101, LHD29), the framework produced many expressible designs (63/64 expressed), with a substantial fraction matching the intended oligomeric states by SEC (33/63) and SEC-MALS (18/63).

5. Structural accuracy was validated by crystallography for multiple designs: C3 trimers (PI25, PI31) and a C4 tetramer (PI57) closely matched design models (Cα RMSD < 1.6 Å), including accurate interface side-chain placement; the resulting folds were also “new-to-nature” by Foldseek comparisons.

6. The approach generalizes to chemical triggers by reusing ligand/metal-dependent PPIs as seeds (often fragmented into many discontinuous segments), enabling conditional C3 assembly for Cu2+ (MC11), cholic acid (CHD04), and venetoclax (LBM10). Measured effective assembly affinities were in the ~100 nM range (e.g., MC11 Kd,eff 137 nM; LBM10 Kd,eff 130 nM).

7. Crystal structures of CHD04 and LBM10 matched their design models and showed ligand occupancy in the engineered pockets, demonstrating that the seeded responsive interface can be transplanted into entirely new oligomer topologies while retaining chemical control.

8. A major functional advance is reversible phosphorylation-controlled oligomerization using a dynamic “phosphoswitch” interface seed: phosphorylation by PKA shifts monomer→oligomer, and λ-phosphatase reverses it back. Single interface-weakening mutations reduced unwanted basal oligomerization while preserving phospho-dependent assembly (PO5s, PO18s).

9. The work also demonstrates multi-input control: introducing a disulfide lock created a system that requires both reducing conditions and phosphorylation to oligomerize, enabling dual-gated assembly behavior in a de novo designed oligomer.

10. Applications go beyond in vitro biophysics: (i) ligand-triggered membrane binding via MinD membrane-targeting sequence fusions (Cu2+ or CHD induces oligomerization-driven avidity on supported lipid bilayers), and (ii) phosphorylation-inducible transcription in HEK293T cells by coupling PO18s trimerization to an HSF1-based reporter, yielding ~6-fold induction (and >14-fold with combined endogenous + engineered PKA activation).

💻Code: https://t.co/XfOyrQXTCQ ; https://t.co/L7pDzceKN7
📜Paper: https://t.co/Oy61XIA0Dl
#ProteinDesign #RFdiffusion #AlphaFold3 #SyntheticBiology #ComputationalBiology #ProteinEngineering #DeNovoDesign #SignalTransduction #Phosphorylation #Nanobiotechnology

[rcsb pdb 💉🧬💻🔬💊🌱🧠🦠 @buildmodels]

Love this graphical abstract for "The Ascent of Miniproteins"
https://t.co/vhZesMp7hN

[Science Magazine @ScienceMagazine]

Some bacteria that are harmful to humans escape elimination by antibiotics because they carry resistance genes. However, antibiotic-susceptible bacterial populations often harbor rare persister cells that survive antibiotic exposure without being resistant. Antibiotic persistence favors recurrent infections and resistance emergence and is a public health threat.

Persister cells are thought to be metabolically dormant. Decreased activity of antibiotic targets would enable them to remain alive when antibiotics are present and to regrow after antibiotic removal.

In a new Science study, researchers report that Escherichia coli persister cells do not simply enter a dormant state upon antibiotic treatment. Instead, genetically identical cells diverge into two physiological states.

Some cells produce membrane vesicles that are loaded with specific proteins, which are taken up by other cells to enhance survival. Therefore, vesicle donors and recipients actively cooperate to benefit the entire bacterial population.

Learn more in a new #SciencePerspective: https://t.co/be5JNwqHJa

[Nilimesh Das @NilimeshDa6026]

Why excite fluorescence when the probe can make its own light?

Visualizing cellular G-quadruplexes with a bioinspired chemiluminescent probe that enables excitation-free imaging of G-quadruplexes in living cells with high contrast and low background.

https://t.co/KSTvpg72G7

[Alena Khmelinskaia @khmelinskaia]

De novo designed oligomers that respond to copper, small molecules, and phosphorylation...
Using a single design strategy? 🧬⚙️
🎉

Excited to share our new bioRxiv preprint—a collaboration between the Khmelinskaia, Correia, Schoeder and a Tinnefeld labs!

https://t.co/8Hdfs52L0E

[Benetton @benenen12345]

古細菌による遺伝暗号の拡張

系統的に離れた古細菌において、本来は終止コドンのTAGが21種類目のアミノ酸ピロリシンのコドンとして利用されていた
ピロリシンは1800種以上のタンパク質に含まれ、この古細菌システムによるピロリシン類自体の大腸菌への導入もできた #BNTNJC
https://t.co/fJ4kKRueFD