Papers nuevos sobre Bioquímica y estructura
91 papers nuevos sobre bioquímica y estructura en los últimos 7 días, dentro de Biología. Acá están los 50 que Pipette considera más valiosos, con el resultado principal en palabras de sus autores.
Lo mejor de la semana
Structural basis of step II spliced leader RNA trans-splicing in trypanosomatid parasites
These structures reveal the molecular mechanism of SL exon ligation and uncover lineage-specific adaptations that remodel the trypanosomatid trans-spliceosome for SL trans-splicing while preserving fundamental spliceosomal chemistry.
Revista con revisión por paresDice ser un gran avanceLate-Stage Posttranslational Assembly of Fosfazinomycins
In this work, we provide the final missing steps in fosfazinomycin biosynthesis by revealing an unexpected engagement of biosynthetic machinery that is typically involved in ribosomally synthesized and post-translationally modified peptides (RiPPs).
PreprintDice ser un gran avanceShield strike shatter in DNA topology and nuclease interactions
Together, these findings establish a nanoscale structural and kinetic framework for how DNA is either degraded or protected under enzymatic stress, with implications for chromatin biology, innate immunity, autoimmune disease, and the design of nuclease-resistant gene delivery systems.
Revista con revisión por paresUso en el mundo realIntegrative structure of norovirus NS3 suggests a role in RNA transport
This model supports a role for NS3 as a candidate membrane-spanning RNA translocase that may couple ATP hydrolysis to genome movement.
Revista con revisión por paresHydrogen sulfide engages catalytic zinc in HDAC6 to modulate an alternative deacetylation pathway
Here we show that H₂S-derived sulfur species engage the catalytic Zn²⁺ center of histone deacetylase 6 (HDAC6) and enhance deacetylase activity under defined conditions.
Revista con revisión por paresChemical Synthesis of Thrombostasin: An Anticoagulant Protein Produced by the Horn Fly Haematobia irritans
Here, we report the first chemical synthesis of native thrombostasin and a hepta-glutamate analogue, together with assessment of their thrombin inhibitory and anticoagulant activity.
PreprintIn situ structure of the flagellar export apparatus reveals membrane remodeling and lipid-mediated coupling between FlhA and the export gate
Together, these findings establish a mechanistic framework for export apparatus assembly and energy transduction, providing broader insights into type III secretion.
Revista con revisión por paresIn Vivo Length Distributions as Mechanistic Fingerprints of Pathological Protein Aggregation
Crucially, the decay rate is determined by the balance between aggregate elongation and removal, providing a direct quantitative readout of these competing processes from a single time point measurement.
PreprintA binuclear copper enzyme platform for enantioconvergent radical (pseudo)halogenation
Herein, we report the systematic investigation and reprogramming of natural copper enzymes to catalyze unnatural free radical (pseudo)halogenation reaction in a highly enantioselective fashion.
PreprintStructural basis of lenacapavir-induced HIV-1 capsid defects during virion maturation
Our structural analyses reveal that LEN alters interhexamer interactions, perturbs the capsid lattice curvature, and thereby prevents the formation of a functional cone-shaped capsid.
Revista con revisión por paresUso en el mundo realBiosensor-enabled single-molecule enzyme activity profiling for function-based molecular counting
Here we establish a biosensor-based framework that integrates genetically encoded fluorescent metabolite biosensors with single-molecule enzyme activity profiling (SEAP), enabling native enzymatic reactions to be monitored without enzyme-specific fluorogenic substrates.
PreprintStructural basis of ligand-selective transcriptional activation in the MerR-family antibiotic resistance regulator AlbA
Here, using an integrative multidisciplinary approach, we define this mechanism and show that albicidin and PBDs elicit different responses.
PreprintUso en el mundo realStructural insights into DHODH-mediated catalysis and drug resistance
Together, our findings provide structural evidence for the ping pong model of catalysis, define the mutational landscape governing inhibitor resistance, and reveal novel structural vulnerabilities in DHODH that can be utilized for future drug development.
PreprintUso en el mundo realArchitecture and Energy Transfer of the Bacterial Photosynthetic Unit
Here, we report cryo-electron microscopy structures of PSU supercomplex assemblies from the phototrophic a-proteobacterium Rhodovulum viride, including an RC-LH1 core associated with one or two peripheral LH2 complexes and a curved LH2 tetramer.
PreprintStructural mechanisms of SAMD9 autoinhibition and pathogenic dysregulation
Together, these findings define the structural basis of SAMD9 autoinhibition and reveal how human GoF mutations disrupt this regulatory mechanism to drive disease.
Revista con revisión por paresExpandable DNA-origami rings as a nanomechanical platform for studying disordered nucleoporins
Our work thus elucidates spatially confined Nup-Nup and Nup-NTR interactions within an NPC-like nanopore, suggests a previously underappreciated role of FG-Nups in modulating NPC dilation, and establishes a generalizable method for studying multivalent interactions among disordered proteins.
PreprintOptical control of membrane mechanics via global and red-light-catalyzed, leaflet-selective photolipid switching
We underscore the biocompatibility of catalysis by demonstrating the effect of leaflet-specific catalyzed perturbations on the ROS-sensitive mechanosensitive peptide ion channel gramicidin A. Our results establish a novel tool for dissecting the role of dynamic leaflet-specific mechanical changes in membrane remodeling and protein function.
PreprintNanophotonic DyeCycling delivers single-molecule FRET beyond photobleaching to identify heterogenous dynamics in DNA and protein systems
Here, we establish nanophotonic DyeCycling, which overcomes photobleaching by reversible fluorophore binding and efficient background suppression using zero-mode waveguides.
PreprintVoltage-sensor conformational microenvironments encode isoform-selective ion channel activation
The findings establish a mechanistic framework in which isoform selectivity arises from VSD conformational microenvironments rather than canonical binding determinants and highlight the voltage sensor as a tunable target for developing selective Kv channel openers.
Revista con revisión por paresMolecular Architecture of the Human GCN1-ABCF3 Ribosome Collision Sensor
Here we report a cryo-EM structure of human GCN1 bound to collided di-ribosomes.
PreprintDiscovery of Covalent Wild-Type Isocitrate Dehydrogenase 1 (IDH1) Inhibitors Targeting Cys269
Together, these findings present a mechanistic rationale for the covalent targeting of wild-type IDH1 and provide structurally validated inhibitors for further development.
PreprintUso en el mundo realLOOP-TAG: massively-parallel measurement of length-dependent protein-mediated DNA looping probabilities by tagmentation in vitro
We describe LOOP-TAG, a massively-parallel method.
PreprintLigand-induced activation of RyR1 in native membranes
Here, we determine high-resolution structures of RyR1 in native sarcoplasmic reticulum membranes by cryo-EM/ET, capturing the conformations along the activation pathway and corner-to-corner interfaces between adjacent RyR1 receptors.
Revista con revisión por paresCalcium induced N-terminal gating and pore collapse in connexin-46/50 gap junctions
Here, using single-particle cryo-EM, we define the Ca²+-dependent gating mechanism of native connexin-46/50 (Cx46/50) gap junction channels.
Revista con revisión por paresSignal peptidase complexes set species-specific rules for signal peptide cleavage
Here, we show that human signal peptides with longer hydrophobic cores efficiently target and translocate nascent proteins in both yeast and human but are frequently left uncleaved in yeast, identifying signal peptide cleavage as a major barrier to cross-species compatibility.
PreprintA bacterial Rhesus transporter retunes a structurally conserved ammonium pore into a reversible nitrogen valve
Instead, it uses the conserved Amt/Mep/Rh pore as a branched transport system in which inward uptake and export-linked transport can be separated genetically and mechanistically.
PreprintMonovalent cations differentially regulate the activity of eukaryotic fluoride channels and impact fluoride resistance
In addition to providing general insight into the mechanism of fluoride channel regulation by monovalent cations, these results identify lithium as a previously unknown environmental antagonist of eukaryotic fluoride export and tie cellular fluoride stress tolerance to the abundance of additional ions in the cellular milieu.
Revista con revisión por paresStructure of Blm10:13S proteasome intermediate reveals parallel assembly pathways for the proteasome core particle
These data suggest a parallel assembly pathway exists for Blm10 proteasomes that does not require sequential activity with Pba1/Pba2.
Revista con revisión por paresTeTIR domains define a new class of animal TIR-like NADase effectors in STAND proteins
TeTIRs thus define a distinct family of animal TIR-like NADases embedded in NACHT-type STAND architectures.
PreprintState-specific binding thermodynamics predicts ligand efficacy across ion-channel families.
Our results demonstrate that state-specific binding thermodynamics provides a robust framework for leveraging ion channel structures of diverse conformational states to elucidate mechanisms of action and to advance ion-channel drug discovery beyond simple affinity measurements, enabling the identification of new chemical matter with desired functional attributes.
PreprintAfirmaciones fuertes, leer con cuidadoUso en el mundo realAcoustofluidic cryo-EM enables in situ particle manipulation for uniform, high-quality cryo-EM specimens
Guided by this physical mechanism, validation using liposomes and apoferritin demonstrates that ACE increases particle density by up to fourfold while preserving structural integrity and improving imaging quality.
Revista con revisión por paresAfirmaciones fuertes, leer con cuidadoProgrammable gold nanoparticle conjugates enable precise AMPA receptor localization at brain synapses by cryo-ET
We use these Fab-AuNP conjugates to locate AMPA receptors and probe their conformation upon desensitization with sub nanometer resolution in tomograms derived from brain slice lamella.
PreprintEmergent catch bonds from slip-like contacts: cooperative force-driven proofreading at receptor--ligand interfaces
We expose this mathematical equivalence and the validity regimes of these reductions and introduce cooperative force-driven proofreading (CFPR), a network-level mechanism where pulling geometry enables contact-zone reorganization and additional nucleation of residue binding contributions, generating emergent catch-like responses from individually slip-like residue binding contributions.
PreprintNegative supercoiling facilitates human TOP3α-mediated decatenation of DNA braids via catenation junction melting
Here, using single-molecule optical tweezers and fluorescence microscopy, we show that negative supercoiling promotes local melting of duplex DNA at DNA-DNA crossings within braided molecules, generating single-stranded DNA that can be engaged by TOP3.
PreprintControl of ice thickness in cryo-EM via confinement
We found that well-designed graphene reservoirs can confine liquid film to an optimal thickness and overcome the limitations posed by liquid film instability, achieving precise control of ice thickness with robust reproducibility and large-area uniformity.
Revista con revisión por paresAfirmaciones fuertes, leer con cuidadoUso en el mundo realINO80 rapidly shuttles nucleosomes between chromatin barriers
These findings identify non-exclusive mechanisms for directional reversal and reveal how long-range hINO80 translocation is converted into boundary-constrained nucleosome repositioning, providing a dynamic framework for understanding nucleosome organization within chromatin.
PreprintDual recognition of negative charge by pleckstrin homology (PH) domains
Thus, PH domains can recognize various patterns of protein negative charge, expanding their potential regulatory roles beyond membrane targeting.
PreprintDynamic Pocketome of Trace Amine-Associated Receptors
The result is a dynamic pocketome map of the TAAR family obtained by an approach transferable to other membrane proteins.
PreprintCarbon nanotubes as the supporting film for cryo-EM specimen preparation
In this study, we introduce carbon nanotubes (CNTs) as a one-dimensional fibrous support material to address this issue.
Revista con revisión por paresAfirmaciones fuertes, leer con cuidadoUso en el mundo realCryo-EM structure of ex vivo Sup35 yeast prion and the factors defining prion phenotype
Here, we show that the different frequency of prion fragmentation is determined by their stability, rather than the efficiency of chaperone binding.
Revista con revisión por paresCryo-EM structures of autoinhibited and RNA-activated ZNFX1 helicase
The cryo-EM structure of the ssRNA-bound ZNFX1 dimer reveals that RNA binding displaces the blocking helix and induces large-scale conformational rearrangements that remodel the helicase core into an active configuration.
Revista con revisión por paresMechanism of GPR84 allosteric modulation at a helix 8–proximate site
We identify a helix 8–proximate allosteric site in the immune-metabolic receptor GPR84 and define how it achieves G i -biased signaling.
Revista con revisión por paresAfirmaciones fuertes, leer con cuidadoTwo Glu/Asp residues cooperatively mediate an early step of ATP hydrolysis in GHKL ATPases MutL and GyrB
These results indicate that the conserved glutamate primarily governs positioning of the nucleophilic water, while activation of this water for catalysis is achieved through cooperative general base function of the two acidic residues.
Revista con revisión por paresConformational Barrier-Driven Flux Redistribution across Competing Catalytic Pathways Unifies Diverse Enzyme Kinetic Regimes
The same underlying landscape can therefore produce qualitatively different kinetic behaviours depending on how conformational exchange and substrate capture partition catalytic flux.
PreprintMolecular basis of DNA polymerase ζ’s reverse transcriptase activity
We present here the cryo-EM structure of yeast Polζ (including Rev1) in the act of reverse transcription, wherein the polymerase molds the replicative end of the bound RNA:DNA hybrid into B-like conformation and retains most contacts seen with DNA:DNA.
Revista con revisión por paresSeven amino acids gate transcriptional activation by a minimal MarA Helix turn-helix DNA-binding domain
These findings establish that a single, correctly dimerized HTH domain is sufficient for both DNA binding and transcriptional activation, providing a structural rationale for short AraC/XylS-like proteins and offering a tuneable scaffold for synthetic biology and novel anti-virulence strategies.
PreprintAfirmaciones fuertes, leer con cuidadoAdaptive Milling: imaging feedback-driven automated fabrication of consistently thin cryo-lamellae
We performed a systematic comparison of the quality of lamellae prepared with Adaptive Polishing and conventional automation, and demonstrate that Adaptive Polishing produces thinner lamellae with greater consistency in thickness, and performs well for in situ cryo-electron tomography.
PreprintSpatially Resolved Nucleated Polymerization: A Free-Boundary Model of Protein Aggregation in Concentrated Solutions
We extend Lumry-Eyring nucleated polymerization to a model in which the monomer is a density field and each aggregate is a region bounded by a level set.
PreprintA Molecular Rotor-Based Platform for Dissecting Protein Phase Separation and Aggregation
Here, we combined fluorescent probes, based on molecular rotors, with fluorescence lifetime imaging microscopy to quantify changes in protein dynamics during phase separation-associated aggregate formation.
PreprintAfirmaciones fuertes, leer con cuidadoActivity-based profiling of bacterial RNA-modifying enzymes reveals species-specific 5-methyluridine modification in Bacillus subtilis 23S rRNA
Taken together, our study establishes a versatile platform for RNA modifying enzyme discovery and characterization in bacteria and illuminates species-specific rRNA modification chemistry in B. subtilis .
Revista con revisión por pares