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Description of the cryo-EM structures of the parathyroid hormone type 1 receptor associated with G_q reveals two distinct extracellular conformations with N-glycans stabilizing a ligand-tilted conformation.

Channelrhodopsins are light-gated ion channels for optogenetics. Here, authors report the 2.7 Å cryo-EM structure of a blue-shifted channelrhodopsin from Klebsormidium nitens, revealing a 6-s-cis retinal configuration and unique C-terminal modulation.

Uncultured open-ocean Asgard archaea can harvest light energy using rhodopsins and diverse hydroxylated carotenoid antennas.

Zucchini has been identified as an endoribonuclease responsible for the maturation of small RNA molecules that protect the genome from the damaging effects of unrestrained expression of mobile elements.

Cryo-EM structures reveal how the lasso peptide binds the ET_B receptor, blocking its activation via key hydrophobic interactions. These findings advance lasso peptides as potential drugs for hard-to-treat cancers and GPCR-targeting therapies.

Several X-ray crystal structures of an H⁺-driven multidrug and toxic compound extrusion (MATE) transporter from Pyrococcus furiosus are presented, whose complex structure with macrocyclic peptides may help facilitate the discovery of efficient inhibitors of MATE transporters.

Determination of the crystal structure of the zebrafish LPA₆ receptor shows that the lipid ligand binds to an unusual ligand-binding pocket in the receptor that is laterally accessible through the membrane.

The crystal structure of the bacterial protein YidC is reported, together with a structure-based functional analysis, providing insight into the role of YidC in inserting single-spanning membrane proteins into the membrane.

A crystal structure of SecY bound to an anti SecY Fab fragment revealing a pre-open state of the channel is presented.

This study presents cryo-EM structures of H₄R–G_i and H₁R–G_i/G_s complexes, revealing distinct histamine recognition, activation mechanisms, and a critical determinant of G protein selectivity in H₁R and H₄R.

CXCR3 and CXCR7 are chemokine receptors involved in cellular migration in physiological and pathophysiological context. Here, the authors present cryo-EM structures of CXCR3 in complex with small molecule agonists and discover their dual-agonism at CXCR7.

Peptide synthesis on the ribosome can be blocked by certain peptide motifs. Here, Ando et al. identify E. coli ribosome arrest peptide PepNL. PepNL forms a mini-hairpin to block translation termination and stop codon readthrough counters this stalling.

CRISPR-Cas9 derived from prokaryotes is a powerful genome editing tool. Here, authors report cryo-EM structure of Cas9-sgRNA-nucleosome complex targeting linker DNA, providing insights into Cas9’s interaction with nucleosomes and its implications for genome editing in chromatin.

P2X receptors are nonselective cation channels that are gated by extracellular ATP. Here the authors present the crystal structure of chicken P2X7 with its bound competitive antagonist TNP-ATP and give mechanistic insights into TNP-ATP dependent inhibition through further computational analysis and electrophysiology measurements.

Ecto-nucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) is a type II transmembrane glycoprotein that hydrolyzes both ATP and cGAMP. Here the authors present the crystal structures of the extracellular ___domain of mouse ENPP1 in complex with 3′3′-cGAMP and the reaction intermediate pA(3′,5′)pG and discuss mechanistic implications.

Molecular 'snapshots' of the MnmA thiouridylase–tRNA complex reveal that during RNA sulphuration, a key α-helix forms around the active site, burying U34 into the catalytic pocket. This 'closed' conformation of the active site ensures that sulphur is incorporated into uridine at the correct place.

A series of crystallographic 'snapshots' of tRNA maturase reveals the molecular changes in the enzyme that holds it in place on the tRNA, accommodating incoming CTP and ATP nucleotides, and allowing repositioning of the active site after each of the first two CMP residues are added.

In this study, the authors report the identification, biochemical characterization and cryo-electron microscopy structure of a phage-encoded miniature type V CRISPR-Cas nuclease in different functional states. This work provides mechanistic insight into CRISPR-Cas12 nucleases and a solid framework for future rational engineering.

Cryo-EM analyses of human LRRC8A show a homohexameric assembly that can adopt two conformations, compact or relaxed, indicating rigid-body motions that might be involved in channel gating.

Adenosine A₃ receptor (A₃R) plays important roles in neurons, heart, and immune cells, and is often overexpressed in tumors. Oshima et al. identify tRNA-derived i⁶A as an A₃R-selective ligand and use cryo-EM to reveal A₃R’s selectivity and activation mechanisms.

Lee et al. report six cryo-EM structures of LAT1 in complex with various substrates and inhibitors, including nanvuranlat (JPH203) under clinical trials. These structures provide insights into the mechanisms of amino acid transport and inhibition, aiding future drug design.

EAAT2 is an amino acid transporter implicated in glutamate homeostasis in brain and therapy resistance of cancer cells. Here, the authors report cryo-EM structures and reveal inhibitory mechanisms via selective inhibitor WAY213613.

SWEET family proteins mediate cellular sugar efflux and exchange through a facilitative diffusion mechanism. Here, Lee et al. shed light on the overall sugar transport cycle of the SemiSWEET uniporter-based structures trapped in both the inward-facing and outward-facing conformations.

Rhodopsin phosphodiesterase (Rh-PDE) hydrolyzes both cAMP and cGMP in a light-dependent manner. Structural and functional analyses of the Rh-PDE from Salpingoeca rosetta reveal unusual rhodopsin topology comprising 8 transmembrane helices (TMs) and suggest that TM0 plays a crucial role in the enzymatic photoactivity.

Vitamin C is an essential nutrient for our daily life, but how it is transported into our bodies remained unclear. Here, authors revealed multiple structures of human vitamin C transporter, providing insights into its molecular mechanisms.

Vacuolar iron transporter 1 (VIT1) is important for iron homeostasis in plants. VIT1 forms a dimeric structure with five membrane-spanning domains, and an ion-translocating pathway of methionine and carboxylate residues at the dimer interface.

GPR103, a GPCR activated by pyroglutamylated RF-amide peptide QRFP, has various physiological functions, such as energy metabolism and appetite regulation. Here, the authors determined the cryoEM structure of the QRFP26- GPR103-Gq complex, revealing its peptide recognition mechanism.

Cryo-electron microscopy structures of the prime editor bound to a prime editing guide RNA and target DNA, in the pre-initiation, initiation and elongation and termination states, provide insights into the mechanism by which prime editing occurs.

The TDF peptide interacts with the leucine-rich repeat receptor-like kinase TDR to regulate meristem differentiation in plants. Here, the authors solve the structure of the extracellular ___domain of TDR in complex with TDIF and propose a mechanism for TDIF recognition.

GPR34 is a GPCR which has an immunomodulatory role and recognizes lysophosphatidylserine (LysoPS) as a putative endogenous ligand. Here, authors report two cryo-EM structures of human GPR34-Gi complex with one of two ligands bound: either the LysoPS analogue S3E-LysoPS, or its derivative M1.

Francisella novicida Cas9 (FnCas9) has low cellular editing ability which limits its therapeutic utilities. Here, the authors rationally engineer the protein to develop enhanced FnCas9 (enFnCas9) variants with high on-target editing efficiency, high precision, broadened target range, and flexible base editing outcomes.

MgtE is an Mg²⁺ transporter involved in Mg²⁺ homeostasis. Here, the authors report that ATP regulates the Mg⁺²-dependent gating of MgtE and use X-ray crystallography combined with functional studies to propose the molecular mechanisms involved in this process.

Here, the authors structurally decipher how Cas12m2 protects against mobile genetic elements by tightly binding invading DNA via a unique arginine-rich cluster and its non-canonical RuvC site.

Cryo-electron microscopy analysis of the Deinococcus radiodurans ISDra2 TnpB in complex with its cognate ωRNA and target DNA provides insights into the mechanism of TnpB function and the evolution of CRISPR–Cas12 effectors.

Light energy transfer from abundant hydroxylated carotenoids to the retinal moiety of widespread light-driven proton pumps is detected.

Outer hair cell electromotility, driven by prestin, is essential for mammalian cochlear amplification. Here, the authors report the cryo-EM structures of thermostabilized prestin in the presence of various anions, providing insight into the mechanisms of mammalian cochlear amplification.

LPA₁ is one of the GPCRs that are drug targets for various diseases. Here the authors report a cryo-EM structure of the active human LPA₁-G_i complex bound to an LPA analog with more potent activity against LPA₁ and clarified the ligand recognition mechanism.

Signalling through the endothelin receptor ET_B, a class A GPCR, induces nitric oxide-mediated vasorelaxation. Here the authors present the crystal structures of the human ET_B receptor bound to the peptide hormone endothelin-3 and in complex with the ET_B-selective partial agonist IRL1620 and discuss mechanistic implications for receptor activation.

The engineered Streptococcus pyogenes Cas9 variant SpCas9-NGv1, known to recognize relaxed NG protospacer adjacent motifs (PAMs) in human cells, can also mediate targeted mutagenesis with NG PAMs in rice and Arabidopsis. When fused with cytidine deaminase, it mediates C-to-T substitutions.

Here, cryo-electron microscopy structures of sodium–glucose cotransporter 2, which is responsible for sugar reabsorption in the kidney and is a target for the treatment of type 2 diabetes, reveal a potential mechanism for cellular sugar uptake.

VCCN1 is a plant homolog of bestrophin channels and tunes photoreaction as a voltage-gated anion channel at thylakoids. Here, authors report the cryo-EM structures and functional features of apple VCCN1, with insights into its activation mechanism.

Cryo-electron microscopy structures of the voltage-gated potassium channel Kv4.2 alone and in complex with auxiliary subunits (DPP6S and/or KChIP1) reveal the distinct mechanisms of these two different subunits in modulating channel activity.

Cryo-electron microscopy structures of Drosophila Dicer-2–R2D2 complexes with and without small interfering RNA reveal how the RNA is presented to Argonaute in the correct orientation for viral gene silencing.

Crystal structures of human endothelin ET_B receptor bound to bosentan and to ET_B-selective derivative provide insight into the basis of antagonism by these drugs.