Resolved Structure Research Articles

A newly designed laser-based time- and angle-resolved photoelectron spectroscopy with a time-of-flight electron analyzer

Angle-resolved photoemission spectroscopy can directly detect the energy and momentum resolved electronic structure of solids, serving as a central role in the discovery and understanding of quantum materials. Here, we report the development of a novel time-resolved ARPES setup equipped with a table-top vacuum ultraviolet laser source with a photon energy of 10.8 eV and a time-of-flight analyzer. The light source is obtained through the generation of ninth harmonics of a 1030 nm Yb fiber-based amplified laser (290 fs, 100 μJ). The photon flux can reach 5 × 1012 photons/s at 333 kHz. We demonstrate its performance in ARPES measurements of the polycrystalline gold film and the electronic structure of the topological insulator Bi2Te3. By introducing a pump beam, we make a pump–probe experiment to detect unoccupied electronic states of Bi2Te3. This setup can achieve an energy resolution of 21.6 meV and a temporal resolution of 296 fs with the tunability of the polarization and repetition rates. This system can provide an important platform to study the non-equilibrium band structure of complex quantum materials with exceptional energy resolution at high repetition rates.

Resolving the Structure of a Guanine Quadruplex in TMPRSS2 Messenger RNA by Circular Dichroism and Molecular Modeling.

The presence of a guanine quadruplex in the opening reading frame of the messenger RNA coding for the transmembrane serine protease 2 (TMPRSS2) may pave the way to original anticancer and host-oriented antiviral strategy. Indeed, TMPRSS2 in addition to being overexpressed in different cancer types, is also related to the infection of respiratory viruses, including SARS-CoV-2, by promoting the cellular and viral membrane fusion through its proteolytic activity. The design of selective ligands targeting TMPRSS2 messenger RNA requires a detailed knowledge, at atomic level, of its structure. Therefore, we have used an original experimental-computational protocol to predict the first resolved structure of the parallel guanine quadruplex secondary structure in the RNA of TMPRSS2, which shows a rigid core flanked by a flexible loop. This represents the first atomic scale structure of the guanine quadruplex structure present in TMPRSS2 messenger RNA.

A comparison of pulse and CW EPR [formula omitted]-relaxation measurements of an inhomogeneously broadened nitroxide spin probe undergoing Heisenberg spin exchange 2. The intercept discrepancy

Experimental confirmation of a theoretical prediction of a non-linear broadening of the spin packets of nitroxide free radicals due to Heisenberg spin exchange at low concentrations, C, is presented. A recent demonstration that spectra with resolved proton hyperfine structure may be analyzed efficiently and accurately was utilized to confirm the theory. As C→0, a plot of the spin-packet line width (SPW) curves downward due to the presence of proton hyperfine couplings that increase the number of distinguishable quantum spin states. At higher C, the broadening is linear with C and the results for the spin exchange rate constant determined from the slope of the broadening of the average spin-packet line width and electron spin echo measurements are in agreement. It is shown that applying modest digital smoothing does not change the values of the SPW. An example of a practical application of these methods to published work is presented, allowing an enigma to be resolved.

Swift J1727.8–1613 Has the Largest Resolved Continuous Jet Ever Seen in an X-Ray Binary

Multiwavelength polarimetry and radio observations of Swift J1727.8–1613 at the beginning of its recent 2023 outburst suggested the presence of a bright compact jet aligned in the north–south direction, which could not be confirmed without high-angular-resolution images. Using the Very Long Baseline Array and the Long Baseline Array, we imaged Swift J1727.8–1613 during the hard/hard-intermediate state, revealing a bright core and a large, two-sided, asymmetrical, resolved jet. The jet extends in the north–south direction, at a position angle of −0.60° ± 0.07° east of north. At 8.4 GHz, the entire resolved jet structure is ∼110(d/2.7kpc)/sini au long, with the southern approaching jet extending ∼80(d/2.7kpc)/sini au from the core, where d is the distance to the source and i is the inclination of the jet axis to the line of sight. These images reveal the most resolved continuous X-ray binary jet, and possibly the most physically extended continuous X-ray binary jet ever observed. Based on the brightness ratio of the approaching and receding jets, we put a lower limit on the intrinsic jet speed of β ≥ 0.27 and an upper limit on the jet inclination of i ≤ 74°. In our first observation we also detected a rapidly fading discrete jet knot 66.89 ± 0.04 mas south of the core, with a proper motion of 0.66 ± 0.05 mas hr−1, which we interpret as the result of a downstream internal shock or a jet–interstellar medium interaction, as opposed to a transient relativistic jet launched at the beginning of the outburst.

The heart of galaxy clusters: Demographics and physical properties of cool-core and non-cool-core halos in the TNG-Cluster simulation

We analyzed the physical properties of the gaseous intracluster medium (ICM) at the center of massive galaxy clusters with TNG-Cluster, a new cosmological magnetohydrodynamical simulation. Our sample contains 352 simulated clusters spanning a halo mass range of 1014 < M500c/M⊙ < 2 × 1015 at z = 0. We focused on the proposed classification of clusters into cool-core (CC) and non-cool-core (NCC) populations, the z = 0 distribution of cluster central ICM properties, and the redshift evolution of the CC cluster population. We analyzed the resolved structure and radial profiles of entropy, temperature, electron number density, and pressure. To distinguish between CC and NCC clusters, we considered several criteria: central cooling time, central entropy, central density, X-ray concentration parameter, and density profile slope. According to TNG-Cluster and with no a priori cluster selection, the distributions of these properties are unimodal, whereby CCs and NCCs represent the two extremes. Across the entire TNG-Cluster sample at z = 0 and based on the central cooling time, the strong CC fraction is fSCC = 24%, compared to fWCC = 60% and fNCC = 16% for weak and NCCs, respectively. However, the fraction of CCs depends strongly on both halo mass and redshift, although the magnitude and even direction of the trends vary with definition. The abundant statistics of simulated high-mass clusters in TNG-Cluster enabled us to match observational samples and make a comparison with data. The CC fractions from z = 0 to z = 2 are in broad agreement with observations, as are the radial profiles of thermodynamical quantities, globally as well as when divided as CC versus NCC halos. TNG-Cluster can therefore be used as a laboratory to study the evolution and transformations of cluster cores due to mergers, AGN feedback, and other physical processes.

Ion Spectroscopy Reveals Structural Difference for Proteins Microhydrated by Retention and Condensation of Water.

Protein ubiquitin in its +7 charge state microhydrated by 5 and 10 water molecules has been interrogated in the gas phase by cold ion UV/IR spectroscopy. The complexes were formed either by condensing water onto the unfolded bare proteins in a temperature-controlled ion trap or by incomplete dehydration of the folded proteins. In the case of cryogenic condensation, the UV spectra of the complexes exhibit a resolved vibrational structure, which looks similar to the spectrum of bare unfolded ubiquitin. The spectra become, however, broad-band with no structure when complexes of the same size are produced by incomplete dehydration under soft conditions of electrospray ionization. We attribute this spectroscopic dissimilarity to the structural difference of the protein: condensing a few water molecules cannot refold the gas-phase structure of the bare ubiquitin, while the retained water preserves its solution-like folded motif through evaporative cooling. This assessment is firmly confirmed by IR spectroscopy, which reveals the presence of free NH and carboxylic OH stretching vibrations only in the complexes with condensed water.

Identification of FDA-approved drugs that induce heart regeneration in mammals.

Targeting Meis1 and Hoxb13 transcriptional activity could be a viable therapeutic strategy for heart regeneration. In this study, we performd an in silico screening to identify FDA-approved drugs that can inhibit Meis1 and Hoxb13 transcriptional activity based on the resolved crystal structure of Meis1 and Hoxb13 bound to DNA. Paromomycin (Paro) and neomycin (Neo) induced proliferation of neonatal rat ventricular myocytes in vitro and displayed dose-dependent inhibition of Meis1 and Hoxb13 transcriptional activity by luciferase assay and disruption of DNA binding by electromobility shift assay. X-ray crystal structure revealed that both Paro and Neo bind to Meis1 near the Hoxb13-interacting domain. Administration of Paro-Neo combination in adult mice and in pigs after cardiac ischemia/reperfusion injury induced cardiomyocyte proliferation, improved left ventricular systolic function and decreased scar formation. Collectively, we identified FDA-approved drugs with therapeutic potential for induction of heart regeneration in mammals.

Discovery of 5-aminopyrido[2,3-d]pyrimidin-7(8H)-one derivatives as new hematopoietic progenitor kinase 1 (HPK1) inhibitors

Hematopoietic progenitor kinase 1 (HPK1) is a negative regulator of T-cell receptor signaling. While HPK1 is considered as a promising target for cancer immunotherapy, no small-molecule HPK1 inhibitors have been approved for cancer treatment. Herein, we report the discovery of a series of new HPK1 inhibitors with a 5-aminopyrido[2,3-d]pyrimidin-7(8H)-one scaffold. The most potent compound 9f inhibited HPK1 kinase activity with an IC50 of 0.32 nM in the time-resolved fluorescence resonance energy transfer (TR-FRET) assays, while displayed reasonable selectivity in a panel of 416 kinases. Cellular engagement of HPK1 by compound 9f was confirmed through the nano-bioluminescence resonance energy transfer (Nano-BRET) experiments. Compound 9f effectively reduced the phosphorylation of the downstream protein SLP-76 in primary peripheral blood mononuclear cells (PBMCs) and human T lymphocytic leukemia Jurkat cells. Compound 9f also enhanced the IL-2 and IFN-γ secretion in PBMCs. Furthermore, the binding mode of compound 9f with HPK1 was confirmed by the resolved cocrystal structure. Taken together, this study provides HPK1 inhibitors with a novel scaffold and clear binding mode for further development of HPK1-targeted therapeutic agents.

Catalytic One-pot Solvent Free Synthesis, Biological Activity, and Docking Study of New Series of 1, 3-thiazolidine-4-one Derivatives Derived from 2- (P-tolyl) Benzoxazol-5-amine.

In this study, a simple triethylammonium salt of phosphoric acid (triethylammonium dihydrogen phosphate) (4) in the liquid state was utilized as an inexpensive, efficient one-pot three components, solvent-free synthesis of thiazolidine-4-one derivatives, with good to excellent yields. Techniques such as FT-IR, 1H-NMR, 13C-NMR, 13C-NMR-DEPT-135, and MS. were used for the structural elucidation. The high biotic efficiency of the newly obtained compounds was confirmed by in vitro antimicrobial action against Gram-positive (S. Aureus), Gram-negative bacteria (P. Aeruginosa and E. Coli) and antifungal activity (C. Albicans) via microplate titer dilution technique. Finally, a molecular docking study was performed with a resolved crystal structure of S. Aureus D-alanine alanyl carrier protein ligase (PDB ID: 7VHV). This investigation aimed to synthesize a new series of thiazolidine-4-one derivatives combined with benzoxazole moiety. Ionic liquid assistance one-pot solvent-free synthesis method used to synthesize a new series of thiazolidine-4-one derivative 10(a-e). Structural identification of new synthesis and biological evaluation via techniques of (IR, 1H-NMR, 13C-NMR, 13C-NMR-DEPT-135, and MS). Ionic liquid is utilized as an inexpensive, efficient one-pot three-component solvent-free synthesis of thiazolidine-4-one derivatives with good to excellent yields. Most of the synthesized compounds showed high biological and anti-fungal activity, in line with the docking study against mentioned microorganism and crystal structure of PDB (ID: 7VHV), respectively.

In Silico analysis of molecular mimic between Der p 23 against allergenic sources

To identify through In Silico analysis the possible molecular mimicry between Der p 23 and antigens from allergenic sources. Identity was sought between Der p 23 and proteins from the mite families Pyroglyphidae, Acaridae, Chortoglyphidae and Echimyopodidae, through PSI-BLAST and They used PRALINE and EMBOSS for the alignments. Antigens with resolved experimental structure were obtained from Protein Data Bank and those not reported were generated using Swiss Model server and ALPHAFOLD 2. Epitope prediction was carried out with the Ellipro server and Pymol 2.3 was used to visualize the 3D models. The analysis between Pyroglyphidae allergens and Der p 23 showed identity with the endochitinase-like protein of D. pteronyssinus, and the type 2 chitin binding domain of D. farinae, with identities between 85 and 100%, with coverage of 100%, and 75% respectively. The allergens Der f 23 and Der p 23 of D. farinae and D. pteronyssinus had 100% coverage with identities of 85.42% and 79.59%, respectively. Among the allergens of Tyrophagus putrescentiae, binding to chitin, oviduct-specific glycoprotein and Cda4p were included, which had identity values corresponding to 40%, 42.22% and 34.78%, with coverage values that did not exceed the 55%. No results were found for Chortoglyphidae and Echimyopodidae. There is molecular mimicry and structural homology between Der P 23 and allergens from allergic sources of the Pyroglyphidae and Acaridae families. Potential epitopes were identified in Der p 23, which could present cross-reactivity with the proteins of the allergenic sources studied, which must be demonstrated in In vitro and In vivo studies. In vitro and in vivo work is needed to demonstrate the results obtained in the In Silico analysis.

Deep Chandra Observation of the Remarkable Ionization Cones of NGC 5252

Seyfert galaxy NGC 5252 harbors enormously extended ionization cones that have been previously detected in the optical and X-ray band, offering a unique opportunity to investigate the interaction between the central active galactic nucleus (AGN) and the surrounding gas in the AGN host galaxy. We present deep Chandra imaging spectroscopy of NGC 5252 with a total exposure time of 230 ks. The morphology in the soft X-rays shows resolved extended structure from the nucleus to a large radial distance, and for the first time we detect the outermost X-ray arc at ∼20 kpc. The X-ray cone mostly follows the direction of the optical ionization cones in the southeast and northwest directions, about 20° misaligned with the major axis of the galactic disk of NGC 5252. Fitting the spectra extracted from radial sectors with photoionization models supports that extended emission is mainly photoionized by the central AGN. We also examine the variation of the photoionization parameter along the radial extension and infer a decreasing ionizing continuum of the central engine by a factor of ∼50 over the past 64,000 yr. These findings are consistent with previous suggestions that NGC 5252 resembles a quasar relic with an M ∼ 109 M ⊙ supermassive black hole that went through a minor merger event and switched to a low accretion rate state.

Vibrational and electronic spectra of protonated vanillin: exploring protonation sites and isomerisation.

Photofragmentation spectra of protonated vanillin produced under electrospray ionisation (ESI) conditions have been recorded in the 3000-3700 cm-1 (vibrational) and 225-460 nm (electronic) ranges, using room temperature IRMPD (infrared multiphoton dissociation) and cryogenic UVPD (ultraviolet photodissociation) spectroscopies, respectively. The cold (∼50 K) electronic UVPD spectrum exhibits very well resolved vibrational structure for the S1 ← S0 and S3 ← S0 transitions, suggesting long excited state dynamics, similar to its simplest analogue, protonated benzaldehyde. The experimental data were combined with theoretical calculations to determine the protonation site and configurational isomer observed in the experiments.

Crystal structure, magnetic and optical investigation, Hirshfeld surface analysis, and DFT calculation of new organic-inorganic hybrid (NH3(CH2)2CO2H)2[MnCl4(OH2)2

A novel hybrid material, blending organic and inorganic components (NH3(CH2)2CO2H)2 [MnCl4(OH2)2], has been successfully synthesized and meticulously examined. This intriguing compound crystalizes in monoclinic system, with C2/c space group. The unit cell dimensions are as follows: a = 21.497 (8) Å, b = 7.212 (2) Å, c = 11.149 Å, β = 109.09 (2)°, with a unit cell containing four entities (Z = 4). The asymmetric unit consisted of a combination of one half of ½[Cl4Mn(OH2)2]2- and an organic + NH3(CH2)2CO2H cation. The structural integrity is upheld through an intricate three-dimensional hydrogen network, serving as a stabilizing force for the crystal lattice.Notably, the resolved structure unveils a stratified arrangement along the b-axis, creating distinct layers within the material, separating the organic and inorganic components. The intricate interplay of intermolecular forces, specifically involving H⋅⋅⋅Cl, O⋅⋅⋅O, and H⋅⋅⋅H interactions, has been thoroughly examined using Hirschfeld surface analysis. Furthermore, we employed Density Functional Theory (DFT) calculations to optimize the molecular structure.To gain deeper insights into its properties, we conducted micro-Raman spectroscopy measurements to elucidate the vibration modes exhibited by the compound. Additionally, the material's characteristics were probed using a Vibrating Sample Magnetometer (VSM), the compound exhibits ferromagnetism. The UV–visible absorbance spectroscopy, providing comprehensive information about its optical properties (energy gap is about 4.0 eV).

Glycans modulate lipid binding in Lili-Mip lipocalin protein: insights from molecular simulations and protein network analyses.

The unique viviparous Pacific Beetle cockroaches provide nutrition to their embryo by secreting milk proteins Lili-Mip, a lipid-binding glycoprotein that crystallises in-vivo. The resolved in-vivo crystal structure of variably glycosylated Lili-Mip shows a classical Lipocalin fold with an eight-stranded antiparallel beta-barrel enclosing a fatty acid. The availability of physiologically unaltered glycoprotein structure makes Lili-Mip a very attractive model system to investigate the role of glycans on protein structure, dynamics, and function. Towards that end, we have employed all-atom molecular dynamics simulations on various glycosylated stages of a bound and free Lili-Mip protein and characterised the impact of glycans and the bound lipid on the dynamics of this glycoconjugate. Our work provides important molecular-level mechanistic insights into the role of glycans in the nutrient storage function of the Lili-Mip protein. Our analyses show that the glycans stabilise spatially proximal residues and regulate the low amplitude opening motions of the residues at the entrance of the binding pocket. Glycans also preserve the native orientation and conformational flexibility of the ligand. However, we find that either deglycosylation or glycosylation with high-mannose and paucimannose on the core glycans, which better mimic the natural insect glycosylation state, significantly affects the conformation and dynamics. A simple but effective distance- and correlation-based network analysis of the protein also reveals the key residues regulating the barrel's architecture and ligand binding characteristics in response to glycosylation.

Insight into electronic, magnetic and optical properties of KMnxNb1-xO3 compound

Density functional theory (DFT) based calculations are performed to study the physical features of Mn doped KNbO3. The spin resolved electronic band structure (BS) and density of states (DOS) are investigated that confirmed the half-metallic ferromagnetic (HMFM) character at x=12.5 and 25% Mn concentration. The energy gap of pure KNbO3 is found to majority influenced by Mn-3d states which introduces new states in the vicinity of Fermi level. The optical features (dielectric function, absorption coefficient, extinction coefficient, refractive index and optical conductivity) are examined to further reveal the role of Mn doping on the KNbO3 compound for optical devices. Finally in magnetic properties, the total magnetic moment of 2.98 and 3.68 μB which is mainly originated from Mn-3d along with weak contribution from K, Nb, and O. Results revealed that KMnxNb1-xO3 compound is a favorable candidate for optoelectronics and spintronics gadgets applications.

Conformational dynamics of α-1 acid glycoprotein (AGP) in cancer: A comparative study of glycosylated and unglycosylated AGP.

α-1 acid glycoprotein (AGP) is one of the most abundant plasma proteins. It fulfills two important functions: immunomodulation, and binding to various drugs and receptors. These different functions are closely associated and modulated via changes in glycosylation and cancer missense mutations. From a structural point of view, glycans alter the local biophysical properties of the protein leading to a diverse ligand-binding spectrum. However, glycans can typically not be observed in the resolved X-ray crystallography structure of AGP due to their high flexibility and microheterogeneity, so limiting our understanding of AGP's conformational dynamics 70 years after its discovery. We here investigate how mutations and glycosylation interfere with AGP's conformational dynamics changing its biophysical behavior, by using molecular dynamics (MD) simulations and sequence-based dynamics predictions. The MD trajectories show that glycosylation decreases the local backbone flexibility of AGP and increases the flexibility of distant regions through allosteric effects. We observe that mutations near the glycosylation site affect glycan's conformational preferences. Thus, we conclude that mutations control glycan dynamics which modulates the protein's backbone flexibility directly affecting its accessibility. These findings may assist in the drug design targeting AGP's glycosylation and mutations in cancer.

Spectra of Rg-water dimers in the region of the D2O ν3 asymmetric stretch (Rg = Ar, Kr, Xe)

Spectra of rare gas (Rg) – D2O dimers (Rg = Ar, Kr, Xe) are studied in the region of the D2O ν3 asymmetric stretch (≈2800 cm−1), using a rapid-scan tunable infrared optical parametric oscillator source to probe a pulsed supersonic slit jet expansion. Three bands are observed in each case, labelled according to the D2O rotational transition with which they correlate as: Σ(101) ← Σ(000), Π(101) ← Σ(000), and Σ(000) ← Σ(101). The Ar-D2O bands exhibit various perturbations and line broadening effects. For Kr-D2O, the Π(101) ← Σ(000) and Σ(000) ← Σ(101) bands are simple and relatively unperturbed with almost no resolved Kr isotope structure, while the Σ(101) ← Σ(000) band is highly perturbed and shows large isotope splittings. This latter perturbation is analyzed in detail with good results. For Xe-D2O, the experimental spectra are unfortunately weaker. Analysis of the Π(101) ← Σ(000) and Σ(000) ← Σ(101) bands is again relatively straightforward, but the Σ(101) ← Σ(000) band is even more perturbed than for Kr-D2O and its analysis proves impossible. Line broadening (for Ar-D2O) and vibrational frequency shift effects are described.

The first mitochondrial genome of Melastoma dodecandrum resolved structure evolution in Melastomataceae and micro inversions from inner horizontal gene transfer

Melastoma dodecandrum is recognized as an ideal industrial subshrub in Melastoma with special characters, like medicinal component, edible fruits, bizarre heteromorphic stamen flowers. Because of strong tolerance to drought and poor land, now it is gradually domesticated into functional economic crops. These special development characters and reported abundant metabolites are suspected to have influence by the mitochondria. To get a better understand of this potential species, we first generated the circle mitochondrial genome with Pacbio-Illumina hybrid sequencing strategy. Finally, the 411,944 bp physical map of M. dodecandrum displayed a long intergenic region segmentation structure and from the comparison with other plant mitogenomes, we unveiled large-scale rearrangements of conserved genes caused by micro inversions. A new insight highlighted the lateral gene transfer from nuclear, chloroplast to mitochondrial genome, consistent fragments captured functional genes like Cytb6f. In the generalized analysis of energy and metabolism genes, we detected a loss of ccmFN and a repeat of cox1 in the whole mitogenome, making it contain relatively complete energy metabolic system. Abnormal selective pressure occurred among the genes in mitogenome and chloroplast, inferring different driving forces of selection existed in the transfer of organic and nuclear genetic materials from hybridization event. This manifested a phylogenetic conflict between the mitochondrial gene and chloroplast gene tree. Eventually, our newly assembled mitogenome will add the knowledge of general trends in mitogenome evolution within dicotyledons and lay solid foundation to the future industrial development.

Apertif 1.4 GHz continuum observations of the Boötes field and their combined view with LOFAR

We present a new image of a 26.5 square degrees region in the Boötes constellation obtained at 1.4 GHz using the Aperture Tile in Focus (Apertif) system on the Westerbork Synthesis Radio Telescope. We use a newly developed processing pipeline that includes direction-dependent self-calibration, which provides a significant improvement in the quality of the images compared to those released as part of the Apertif first data release. For the Boötes region, we mosaicked 187 Apertif images and extracted a source catalog. The mosaic image has an angular resolution of 27 × 11.5″ and a median background noise of 40 μJy beam−1. The catalog has 8994 sources and is complete down to the 0.3 mJy level. We combined the Apertif image with LOFAR images of the Boötes field at 54 and 150 MHz to study the spectral properties of the sources. We find a spectral flattening toward sources with a low flux density. Using the spectral index limits from Apertif nondetections, we derive that up to 9% of the sources have ultrasteep spectra with a slope below −1.2. A steepening of the spectral index with increasing redshift is also seen in the data, which shows a different dependence for the low-and high-frequency spectral index. The explanation probably is that a population of sources has concave radio spectra with a turnover frequency of about the LOFAR band. Additionally, we discuss cases of individual extended sources with an interesting resolved spectral structure. With the improved pipeline, we aim to continue to process data from the Apertif wide-area surveys and release the improved 1.4-GHz images of several well-known fields.

Structure of the Major G-Quadruplex in the Human EGFR Oncogene Promoter Adopts a Unique Folding Topology with a Distinctive Snap-Back Loop.

EGFR tyrosine kinase inhibitors have made remarkable success in targeted cancer therapy. However, therapeutic resistance inevitably occurred and EGFR-targeting therapy has been demonstrated to have limited efficacy or utility in glioblastoma, colorectal cancer, and hepatocellular carcinoma. Therefore, there is a high demand for the development of new targets to inhibit EGFR signaling. Herein, we found that the EGFR oncogene proximal promoter sequence forms a unique type of snap-back loop containing G-quadruplex (G4), which can be targeted by small molecules. For the first time, we determined the NMR solution structure of this snap-back EGFR-G4, a three-tetrad-core, parallel-stranded G4 with naturally occurring flanking residues at both the 5'-end and 3'-end. The snap-back loop located at the 3'-end region forms a stable capping structure through two stacked G-triads connected by multiple potential hydrogen bonds. Notably, the flanking residues are consistently absent in reported snap-back G4s, raising the question of whether such structures truly exist under in vivo conditions. The resolved EGFR-G4 structure has eliminated the doubt and showed distinct structural features that distinguish it from the previously reported snap-back G4s, which lack the flanking residues. Furthermore, we found that the snap-back EGFR-G4 structure is highly stable and can form on an elongated DNA template to inhibit DNA polymerase. The unprecedented high-resolution EGFR-G4 structure has thus contributed a promising molecular target for developing alternative EGFR signaling inhibitors in cancer therapeutics. Meanwhile, the two stacked triads may provide an attractive site for specific small-molecule targeting.