Munc13-4–STX7 inhibitors impair endosomal TLR activation and systemic inflammation - Nature Chemical Biology Endosomal Toll-like receptors (TLRs) are central to the innate immune response but their overactivation can cause systemic inflammation and disease. Now, new small molecules targeting the interaction ...

Inhibitors of Munc13-4-syntaxin 7, essential for endosomal maturation, impair endosomal TLR overactivation and systemic inflammation

www.nature.com/articles/s41...

FYI, the first transparent peer review file @natchembio.nature.com has been published with this paper 👀 Yes, we publish them now if the authors elect to!

Structures of ALG3/9/12 reveal the assembly logic of the N-glycan oligomannose core - Nature Chemical Biology Three endoplasmic reticulum luminal mannosyltransferases ALG3, ALG9 and ALG12 catalyze the synthesis of the branched mannose core in N-glycans in four distinct steps. Now, cryo-electron microscopy str...

The three enzymes ALG3, ALG9, and ALG12 catalyze the synthesis of the branched mannose core in N-glycans in four distinct steps. Now, their structures reveal the molecular logic of oligomannose core assembly #glycotime

www.nature.com/articles/s41...

Very cool biology involving 1) extracellular condensates made of 2) glycans and polyamines from 3) immune cells

🎉🎉 Our paper on temperature-dependent protein control using AsLOV2 variants is now published at @natchembio.nature.com: www.nature.com/articles/s41... including some new insights from extend variant characterizations.

Uncovering bacterial pseudaminylation with pan-specific antibody tools - Nature Chemical Biology Pseudaminic acids (Pse) are a family of carbohydrates found within bacterial lipopolysaccharides, capsular polysaccharides and glycoproteins. Now, monoclonal antibodies have been developed that recogn...

Monoclonal antibodies against pseudaminic acid (Pse) – present in bacterial LPS, capsular polysaccharides, and glycoproteins – have been developed that enable Pse glycoproteome profiling and show therapeutic potential #glycotime

www.nature.com/articles/s41...

Functional analysis of O-GlcNAcylation by networking of OGT interactors and substrates - Nature Chemical Biology Functional studies of O-GlcNAcylation have often focused on individual modifications. Now, a systems-level approach has identified simultaneous O-GlcNAcylation events that coordinate cellular activiti...

Functional studies of O-GlcNAcylation have often focused on individual modifications. Now, a systems-level approach has identified simultaneous O-GlcNAcylation events that coordinate cellular activities and tissue-specific functions #glycotime

www.nature.com/articles/s41...

Out now in @natchembio.nature.com: Xylosyltransferase engineering to manipulate proteoglycans in mammalian cells 🎉 www.nature.com/articles/s41... check out the press release below! #glycotime

Associate or Senior Editor, Nature Chemical Biology Job Title: Associate or Senior Editor, Nature Chemical Biology Organization: Nature Portfolio Location: New York, Washington DC, Jersey City, Beijing or Shanghai – Hybrid working Model Closing date: D...

Job vacancy: Nature Chemical Biology is hiring

Nature Chemical Biology is seeking an Associate or Senior Editor. This is a permanent full-time position within the editorial team. The vacancy is for one of the offices based in USA or China.
springernature.wd3.myworkdayjobs.com/en-US/Spring...

Temporal photoproximity labeling of ligand-activated EGFR neighborhoods using MultiMap - Nature Chemical Biology A multiscale photoproximity labeling proteomics workflow captures dynamic neighborhoods of extracellular and intracellular epidermal growth factor (EGF) receptor interactomes during early, middle and ...

A new paper from @zhilindseylin.bsky.social @jimwellsucsf.bsky.social and colleagues presents temporal mapping of extracellular and intracellular neighborhoods of a protein of interest with MultiMap photoproximity labeling proteomics, here applied to EGFR

www.nature.com/articles/s41...

IDR-induced CAR condensation improves the cytotoxicity of CAR-Ts against low-antigen cancers - Nature Chemical Biology Low-antigen-expressing cancers are a challenge to existing chimeric antigen receptor (CAR)-T cell-based therapies. Now, it has been shown that fusion of intrinsically disordered regions to CARs induces CAR condensation and enhances antigen sensitivity and killing activity of CAR-T cells.

The fusion of intrinsically disordered regions to CARs enhances CAR-T signaling by inducing CAR condensation and enhances CAR sensitivity to low-antigen-expressing cancer cells

www.nature.com/articles/s41...

I loved this simulation-guided paper with reaaally state-of-the-art simulations at first sight 😍

Molecular basis for the regulation of membrane proteins through preferential lipid solvation - Nature Chemical Biology Static protein structures can capture the association of lipids, but it is unclear whether the association is due to lipids acting as long-lived ligands or the solvation of preferred lipids around the protein. A computational-experimental framework has now shown that for the protein CLC-ec1, it is the change in lipid solvation energies that drives dimerization, with preferred lipids around the protein modulating this driving force.

Are the lipids associated with static protein structures there as long-lived ligands or an effect of preferential solvation? This computational-experimental framework shows the way! #lipidtime #compchem

www.nature.com/articles/s41...

Engineering synthetic agonists for targeted activation of Notch signaling - Nature Chemical Biology The development of soluble Notch agonists is a challenge because of the mechanical forces needed to activate Notch receptors. Here, bispecific Notch agonist proteins were designed that ‘pull’ on and activate Notch receptors in the presence of desired biomarkers.

Engineered bispecific Notch agonists “pull” on and mechanically activate Notch receptors in the presence of desired biomarkers

www.nature.com/articles/s41...

Leaflet-specific phospholipid imaging using genetically encoded proximity sensors - Nature Chemical Biology An approach combining bioorthogonal chemistry with genetically encoded fluorogen-activating proteins enables subcellular imaging of phospholipids and glycans, as well as the visualization of lipid tra...

Very excited to share new work out today in @natchembio.nature.com on a new approach - FACES - for selectively imaging of phospholipids and other biomolecules at spatial resolutions down to individual membrane leaflets (1/n) www.nature.com/articles/s41...

Real-time visualization of STAT activation in live cells using genetically encoded biosensors - Nature Chemical Biology The signal transducer and activator of transcription (STAT) family proteins are attractive drug targets but tools to monitor their activation are lacking. Now, STAT biosensors have been developed for ...

The design of STAT biosensors enables real-time tracking of STAT activation in live cells, inhibitor screening, and probing the activity of cancer-associated STAT mutants

www.nature.com/articles/s41...

An unbiased proteomic platform for ATE1-based arginylation profiling - Nature Chemical Biology Arginylation is a post-translational modification that is difficult to distinguish from arginine residues using mass spectrometry. Now a method has been developed to profile protein arginylation ex vi...

Arginylation is a post-translational modification that is difficult to distinguish from arginine residues using mass spec. Now a method has been developed to profile protein arginylation ex vivo

www.nature.com/articles/s41...

Toast with chicken liver and foie gras mousse and blueberries

Octopus with crispy gnocchi and romesco

Mezzi rigatoni with fennel sausage ragu

Pork chop in beurre blanc sauce, dill, and trout roe

The Red Hen in DC for Italian food. I had to wait a month for the reservation! Worth it

Structure-guided phage display discovery of antibodies for (S)Tn-glycans in protein context - Nature Chemical Biology Structural studies of certain Tn and STn antigen-targeting antibodies reveal that their VH and VL domains recognize the glycan antigen and the adjacent peptide region, respectively, enabling a VH doma...

#glycotime #immunology Structure-guided design rules for antibodies targeting cancer antigens with Tn and STn epitopes

www.nature.com/articles/s41...

Mechanism of capsaicin entry into buried vanilloid sites in TRPV1 - Nature Chemical Biology The primary entry route of vanilloid ligands to the vanilloid-binding site in transient receptor potential vanilloid 1 (TRPV1) is found to be a distinct and targetable hydrophobic pathway at the TRPV1...

A new paper reports that the primary mechanism of capsaicin entry into the vanilloid-binding site of TRPV1 is a targetable hydrophobic tunnel at the TRPV1-membrane interface

www.nature.com/articles/s41...

Protein β-O-glucosylation by Legionella LtpM through short consensus sequons G-T/S and S-G - Nature Chemical Biology Legionella effector LtpM is found to recognize short two-residue sequons, enabling site-specific O-glucosylation with minimal perturbations to a target protein, and is used to show that O-glucose can ...

#glycotime Legionella effector LtpM is found to recognize strict two-residue sequons for site-specific O-glucosylation with minimal perturbations to a target protein and is used to show that O-glucose can act as a constitutively active O-GlcNAc mimic

www.nature.com/articles/s41...

Molecular recording of cellular protein kinase activity with chemical labeling - Nature Chemical Biology Molecular recorders based on kinase activity-dependent protein labeling track specific kinase activities to understand their link to cellular phenotypes in heterogeneous cell populations and in vivo.

Molecular recording of cellular protein kinase activity with chemical labeling:

www.nature.com/articles/s41...

Congratulations to De-en Sun and the entire team.

Cysteine allostery and autoinhibition govern human STING oligomer functionality - Nature Chemical Biology Palmitoylation at C64 in stimulator of interferon genes (STING) is reported and, along with engagement of C91, is involved in dynamic cross talk with C148 to alter STING oligomer states and ultimately...

The newest paper from the lab is now out @natchembio.nature.com! A hard-won effort by Rebecca and @xujunc.bsky.social uncovers a previously undescribed post-translationally modified site that regulates STING signaling and proposes a new strategy for inhibition.

www.nature.com/articles/s41...

oh god 😖 🤦🏻‍♂️

Accurate de novo design of high-affinity protein-binding macrocycles using deep learning - Nature Chemical Biology A method for de novo design of peptide macrocyles called RFpeptides has been developed. RFpeptides is an extension of RoseTTAFold2 and RFdiffusion and combines structure prediction and protein backbon...

A new paper from the Institute for Protein Design at UW presents RFpeptides, an extension of RoseTTAFold2 and RFdiffusion for de novo design of macrocyclic peptide binders

www.nature.com/articles/s41...

Functional targeting of membrane transporters and enzymes to peroxisomes - Nature Chemical Biology A modular protein engineering strategy was developed to shuttle transporters and integral membrane enzymes folded in the endoplasmic reticulum to the peroxisomal membrane. This approach expands the re...

Another cool protein eng. paper for you -- Designed "chauffeurs" shuttle transporters and integral membrane enzymes folded in the ER to the peroxisomal membrane. This expands the repertoire of biosynthetic pathways that can be compartmentalized in the peroxisome

www.nature.com/articles/s41...

and check out the associated News & Views by Yang Zhou, Xiaoding Ma, and Haifeng Ye on the innovations of this chemically induced proximity system called SAMBA
www.nature.com/articles/s41...

Repurposing salicylic acid as a versatile inducer of proximity - Nature Chemical Biology A highly compact chemically induced proximity system dependent on salicylic acid or aspirin enables control of biological processes and cellular therapeutics using an over-the-counter drug with minima...

A highly compact chemically induced proximity system dependent on salicylic acid or aspirin enables control of biological processes and cellular therapeutics using an over-the counter drug with minimal side effects

www.nature.com/articles/s41...

A SAMBA for chemically induced proximity - Nature Chemical Biology SAMBA, a new chemically induced proximity system, overcomes the cost, complexity and reversibility challenges of such systems by precisely controlling protein interactions in a biocompatible manner me...

and check out the associated News & Views by Yang Zhou, Xiaoding Ma, and Haifeng Ye on the innovations of this chemically induced proximity system called SAMBA

www.nature.com/articles/s41...

“if it is allowed…” 😞