Direct Tumor Killing and Immunotherapy through Anti-SerpinB9 Therapy.

Cancer therapies kill tumors either directly or indirectly by evoking immune responses and have been combined with varying levels of success. Here, we describe a paradigm to control cancer growth that is based on both direct tumor killing and the triggering of protective immunity. Genetic ablation of serine protease inhibitor SerpinB9 (Sb9) results in the death of tumor cells in a granzyme B (GrB)-dependent manner. Sb9-deficient mice exhibited protective T cell-based host immunity to tumors in association with a decline in GrB-expressing immunosuppressive cells within the tumor microenvironment (TME). Maximal protection against tumor development was observed when the tumor and host were deficient in Sb9. The therapeutic utility of Sb9 inhibition was demonstrated by the control of tumor growth, resulting in increased survival times in mice. Our studies describe a molecular target that permits a combination of tumor ablation, interference within the TME, and immunotherapy in one potential modality.

Recurrent SMARCB1 Mutations Reveal a Nucleosome Acidic Patch Interaction Site That Potentiates mSWI/SNF Complex Chromatin Remodeling.

Mammalian switch/sucrose non-fermentable (mSWI/SNF) complexes are multi-component machines that remodel chromatin architecture. Dissection of the subunit- and domain-specific contributions to complex activities is needed to advance mechanistic understanding. Here, we examine the molecular, structural, and genome-wide regulatory consequences of recurrent, single-residue mutations in the putative coiled-coil C-terminal domain (CTD) of the SMARCB1 (BAF47) subunit, which cause the intellectual disability disorder Coffin-Siris syndrome (CSS), and are recurrently found in cancers. We find that the SMARCB1 CTD contains a basic α helix that binds directly to the nucleosome acidic patch and that all CSS-associated mutations disrupt this binding. Furthermore, these mutations abrogate mSWI/SNF-mediated nucleosome remodeling activity and enhancer DNA accessibility without changes in genome-wide complex localization. Finally, heterozygous CSS-associated SMARCB1 mutations result in dominant gene regulatory and morphologic changes during iPSC-neuronal differentiation. These studies unmask an evolutionarily conserved structural role for the SMARCB1 CTD that is perturbed in human disease.

Viruses inhibit TIR gcADPR signalling to overcome bacterial defence.

The Toll/interleukin-1 receptor (TIR) domain is a key component of immune receptors that identify pathogen invasion in bacteria, plants and animals1-3. In the bacterial antiphage system Thoeris, as well as in plants, recognition of infection stimulates TIR domains to produce an immune signalling molecule whose molecular structure remains elusive. This molecule binds and activates the Thoeris immune effector, which then executes the immune function1. We identified a large family of phage-encoded proteins, denoted here as Thoeris anti-defence 1 (Tad1), that inhibit Thoeris immunity. We found that Tad1 proteins are 'sponges' that bind and sequester the immune signalling molecule produced by TIR-domain proteins, thus decoupling phage sensing from immune effector activation and rendering Thoeris inactive. Tad1 can also efficiently sequester molecules derived from a plant TIR-domain protein, and a high-resolution crystal structure of Tad1 bound to a plant-derived molecule showed a unique chemical structure of 1 ''-2' glycocyclic ADPR (gcADPR). Our data furthermore suggest that Thoeris TIR proteins produce a closely related molecule, 1''-3' gcADPR, which activates ThsA an order of magnitude more efficiently than the plant-derived 1''-2' gcADPR. Our results define the chemical structure of a central immune signalling molecule and show a new mode of action by which pathogens can suppress host immunity.

Modulating TRADD to restore cellular homeostasis and inhibit apoptosis.

Cell death in human diseases is often a consequence of disrupted cellular homeostasis. If cell death is prevented without restoring cellular homeostasis, it may lead to a persistent dysfunctional and pathological state. Although mechanisms of cell death have been thoroughly investigated1-3, it remains unclear how homeostasis can be restored after inhibition of cell death. Here we identify TRADD4-6, an adaptor protein, as a direct regulator of both cellular homeostasis and apoptosis. TRADD modulates cellular homeostasis by inhibiting K63-linked ubiquitination of beclin 1 mediated by TRAF2, cIAP1 and cIAP2, thereby reducing autophagy. TRADD deficiency inhibits RIPK1-dependent extrinsic apoptosis and proteasomal stress-induced intrinsic apoptosis. We also show that the small molecules ICCB-19 and Apt-1 bind to a pocket on the N-terminal TRAF2-binding domain of TRADD (TRADD-N), which interacts with the C-terminal domain (TRADD-C) and TRAF2 to modulate the ubiquitination of RIPK1 and beclin 1. Inhibition of TRADD by ICCB-19 or Apt-1 blocks apoptosis and restores cellular homeostasis by activating autophagy in cells with accumulated mutant tau, α-synuclein, or huntingtin. Treatment with Apt-1 restored proteostasis and inhibited cell death in a mouse model of proteinopathy induced by mutant tau(P301S). We conclude that pharmacological targeting of TRADD may represent a promising strategy for inhibiting cell death and restoring homeostasis to treat human diseases.

Evidence for Two-Dimensional Weyl Fermions in Air-Stable Monolayer PtTe1.75.

The Weyl semimetals represent a distinct category of topological materials wherein the low-energy excitations appear as the long-sought Weyl Fermions. Exotic transport and optical properties are expected because of the chiral anomaly and linear energy-momentum dispersion. While three-dimensional Weyl semimetals have been successfully realized, the quest for their two-dimensional (2D) counterparts is ongoing. Here, we report the realization of 2D Weyl Fermions in monolayer PtTe1.75, which has strong spin-orbit coupling and lacks inversion symmetry, by combined angle-resolved photoemission spectroscopy, scanning tunneling microscopy, second harmonic generation, X-ray photoelectron spectroscopy measurements, and first-principles calculations. The giant Rashba splitting and band inversion lead to the emergence of three pairs of critical Weyl cones. Moreover, monolayer PtTe1.75 exhibits excellent chemical stability in ambient conditions, which is critical for future device applications. The discovery of 2D Weyl Fermions in monolayer PtTe1.75 opens up new possibilities for designing and fabricating novel spintronic devices.

THz spectrum processing method based on optimal wavelet selection.

Terahertz spectrum is easily interfered by system noise and water-vapor absorption. In order to obtain high quality spectrum and better prediction accuracy in qualitative and quantitative analysis model, different wavelet basis functions and levels of decompositions are employed to perform denoising processing. In this study, the terahertz spectra of wheat samples are denoised using wavelet transform. The compound evaluation indicators (T) are used for systematically analyzing the quality effect of wavelet transform in terahertz spectrum preprocessing. By comparing the optimal denoising effects of different wavelet families, the wavelets of coiflets and symlets are more suitable for terahertz spectrum denoising processing than the wavelets of fejer-korovkin and daubechies, and the performance of symlets 8 wavelet basis function with 4-level decomposition is the optimum. The results show that the proposed method can select the optimal wavelet basis function and decomposition level of wavelet denoising processing in the field of terahertz spectrum analysis.

Significance of Gastrokine-1 Polymorphism Rs4254535 as a Prognostic Marker and its Association with Clinical Characteristics in Chinese Lung Cancer Patients.

Background: The single nucleotide polymorphism (SNP) of Gastrokine-1 (GKN1) is associated with lung cancer but its association with prognosis is not clear. Methods: Genomic DNA was extracted from the blood samples of 888 patients with lung cancer. The association between GKN1 polymorphism rs4254535 and prognostic was analyzed by the Kaplan-Meier (KM) method, Log-rank test, and Cox proportional hazards model. Results: In females and patients diagnosed with late-stage lung cancer, the CC genotype (CC vs TT, adjusted odds ratio [HR] = 0.57, 95% Confidence Interval [CI]: 0.33-0.99, P = 0.045; HR = 0.66, 95% CI: 0.48-0.92, P = 0.014) and recessive CC genotype (CC vs TT + TC, HR = 0.55, 95% CI: 0.32-0.94, P = 0.028; HR = 0.64, 95% CI: 0.47-0.89, P = 0.006) of rs4254535 conferred a better prognosis, compared with the TT and TT + TC genotype. Rs4254535 dominate TC + CC genotype, recessive CC genotype, and C allele who were adenocarcinoma patients had a significantly better prognosis. The recessive CC genotype of non-smoking patients has a better prognosis, compared to the TT + TC genotype. Additionally, in the dominant TT + TC genotype and C allele, no family history patients had a significantly better prognosis, compared to the TT genotype. Conclusion: For lung cancer patients, GKN1 polymorphism rs4254535 may be a protective genetic marker and predicts the prognosis of lung cancer patients.

Glyco-signatures in patients with advanced lung cancer during anti-PD-1/PD-L1 immunotherapy.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1/programmed cell death ligand-1 (PD-1/PD-L1) have significantly prolonged the survival of advanced/metastatic patients with lung cancer. However, only a small proportion of patients can benefit from ICIs, and clinical management of the treatment process remains challenging. Glycosylation has added a new dimension to advance our understanding of tumor immunity and immunotherapy. To systematically characterize anti-PD-1/PD-L1 immunotherapy-related changes in serum glycoproteins, a series of serum samples from 12 patients with metastatic lung squamous cell carcinoma (SCC) and lung adenocarcinoma (ADC), collected before and during ICIs treatment, are firstly analyzed with mass-spectrometry-based label-free quantification method. Second, a stratification analysis is performed among anti-PD-1/PD-L1 responders and non-responders, with serum levels of glycopeptides correlated with treatment response. In addition, in an independent validation cohort, a large-scale site-specific profiling strategy based on chemical labeling is employed to confirm the unusual characteristics of IgG N-glycosylation associated with anti-PD-1/PD-L1 treatment. Unbiased label-free quantitative glycoproteomics reveals serum levels' alterations related to anti-PD-1/PD-L1 treatment in 27 out of 337 quantified glycopeptides. The intact glycopeptide EEQFN 177STYR (H3N4) corresponding to IgG4 is significantly increased during anti-PD-1/PD-L1 treatment (FC=2.65, P=0.0083) and has the highest increase in anti-PD-1/PD-L1 responders (FC=5.84, P=0.0190). Quantitative glycoproteomics based on protein purification and chemical labeling confirms this observation. Furthermore, obvious associations between the two intact glycopeptides (EEQFN 177STYR (H3N4) of IgG4, EEQYN 227STFR (H3N4F1) of IgG3) and response to treatment are observed, which may play a guiding role in cancer immunotherapy. Our findings could benefit future clinical disease management.

Wheat Stripe Rust Inoculum from the Southwest Dispersed to the East Huang-Huai-Hai Region through Southern Anhui in China.

Stripe rust, caused by Puccinia striiformis f. sp. tritici, is a continuous threat to global wheat production. In 2021, the epidemic of wheat stripe rust in China affected approximately 4.5 million hectares, resulting in severe yield losses. When confronted with the epidemic, tracing the sources of the pathogen can offer valuable insights for disease prevention and control. This study was conducted to analyze the genetic structure, aerodynamics, geographical features, and cultivation practices of the pathogen population in various wheat-producing regions, and to further reveal the spread patterns of the stripe rust pathogens in China. The findings indicated an overall trend of the pathogen dissemination from the west to the east. The pathogen was primarily spread from the northwestern region to the Huang-Huai-Hai region through the Guanzhong Plain and the NanXiang Plain. Meanwhile, the pathogen was also spread eastward from the southwestern region to the lower reaches of the Yangtze River, utilizing the Jianghan Plain as a bridge and the Yangtze River Valley in southwestern Anhui as the main pathway. Furthermore, the pathogen spread northward into Shandong under the driving force of the southeast winds. The findings of this study may provide valuable insights for the integrated management of wheat stripe rust in China.

Realization of a Two-Dimensional Checkerboard Lattice in Monolayer Cu2N.

Two-dimensional checkerboard lattice, the simplest line-graph lattice, has been intensively studied as a toy model, while material design and synthesis remain elusive. Here, we report theoretical prediction and experimental realization of the checkerboard lattice in monolayer Cu2N. Experimentally, monolayer Cu2N can be realized in the well-known N/Cu(100) and N/Cu(111) systems that were previously mistakenly believed to be insulators. Combined angle-resolved photoemission spectroscopy measurements, first-principles calculations, and tight-binding analysis show that both systems host checkerboard-derived hole pockets near the Fermi level. In addition, monolayer Cu2N has outstanding stability in air and organic solvents, which is crucial for further device applications.

Construction of Ternary Bismuth-Based Heterojunction by Using (BiO)2 CO3 as Electron Bridge for Highly Efficient Degradation of Phenol.

Inspired by nature, it has been considered an effective approach to design artificial photosynthetic system by fabricating Z-scheme photocatalysts to eliminate environmental issues and alleviate the global energy crisis. However, the development of low cost, environment-friendly, and high-efficient photocatalysts by utilizing solar energy still confronts huge challenge. Herein, we constructed a Bi2 O3 /(BiO)2 CO3 /Bi2 MoO6 ternary heterojunction via a facile solvothermal method and calcination approach and used it as a photocatalyst for the degradation of phenol. The optimized Bi2 O3 /(BiO)2 CO3 /Bi2 MoO6 heterojunction delivers a considerable activity for phenol photodegradation with an impressive removal efficiency of 98.8 % and about total organic carbon (TOC) of 68 % within 180 min under visible-light irradiation. The excellent photocatalytic activity was ascribed to the formation of a Z-scheme heterojunction, more importantly, the presence of (BiO)2 CO3 as an electron bridge greatly shortens the migration distance of photogenerated electron from ECB of Bi2 O3 to EVB of Bi2 MoO6 , thus prolonging the lifetime of photogenerated electrons, which is verified by trapping experiments, electron spin-resonance spectroscopy (ESR) results, and density functional theory (DFT) calculations. This work provides a potential strategy to fabricate highly efficient Bi-based Z-scheme photocatalysts with wide application prospects in solar-to-fuel conversion and environmental protection.

The information-motivation-behavioral skills (IMB) model of antiretroviral therapy (ART) adherence among people living with HIV in Shanghai.

The Information-Motivation-Behavioral skills (IMB) model of antiretroviral therapy (ART) adherence was applied in people living with HIV/AIDS in Shanghai, China to understand how adherence-related information, motivation and behavioral skills would affect ART adherence. The LifeWindows Information-Motivation-Behavioral Skills ART Adherence Questionnaire (LW-IMB-AAQ) was translated into Chinese and used. The IMB model was then implemented by testing standardized path estimates with standard model fitness indices in the participants. 426 participants from 11 community centres in Putuo district of Shanghai were recruited, of which 95.3% reported a high level of adherence (>95% adherence). The fitness indices of the final adjusted model were χ2 = 6.110, df = 7, p = 0.527(>0.05), CFI = 1.000(>0.9) and RMSEA = 0.000 (<0.08). In the model, information, which was separated into two sections (the perceived effect of ART on health and knowledge about ART medication), had an indirect effect on the ART adherence through behavioral skills, while motivation did not have such an effect. Neither information nor motivation had a direct effect on ART adherence. In addition, motivation was related to the two sections of information. The feasibility of the IMB model of ART adherence is verified by its application to predictive of adherence-related behaviors among HIV+ patients in this study.

Metal-organic framework derived CdSe wrapped with rGO for enhanced lithium storage performance.

Considering the advantages of MOF-based, CdSe-based, and rGO-based materials, CdSe nanoparticles encapsulated with rGO (CdSe@rGO) were synthesized by a metal-organic framework derived method. CdSe nanoparticles encapsulated with rGO can effectively tolerate volume expansion and improve electrical conductivity, leading to excellent cycling stability (396 mAh g-1at 0.3 A g-1after 200 cycles, 311 mAh g-1at 0.5 A g-1after 500 cycles), and rate performance (562 mAh g-1at 0.1 A g-1and 122.2 mAh g-1at 4 A g-1) for lithium-ion storage. This strategy for preparing metal selenides protected by carbon layers can be extended to the design of other high-performance materials.

Prognostic implications of the EGFR polymorphism rs763317 and clinical variables among young Chinese lung cancer population.

The 5-year survival rate for patients with lung cancer, the world's second most frequent malignant tumor, is less than 20%, and its prognosis cannot be clearly predicted. Our aim was to analyze the epidermal growth factor receptor (EGFR) rs763317 (G>A) single nucleotide polymorphism and its association with prognosis in Chinese Han lung cancer patients. 839 patients with primary lung cancer were recruited, and genomic DNA was extracted and genotyped by SNPscan. Kaplan-Meier technique and multivariate Cox proportional hazards model were used to analyze the association between prognosis and EGFR polymorphism rs763317. A significant association after stratification by age, significantly increased lung cancer risk was associated with the AA homozygous genotype of rs763317 (adjusted hazard ratio = 2.53, 95% CI: 1.31-4.88, p=0.005), and conferred a poor survival for lung cancer patients (MST: median survival time: 13.6 months) compared with GG genotype (MST: 41.5 months), and in the recessive model AA genotype (AA vs. GG + GA; adjusted hazard ratio = 2.57, 95% CI: 1.34-4.93, p=0.004) who were young (<60 years) had a significantly increased risk of death. The EGFR polymorphism rs763617 might serve as a significant genetic marker for predicting the prognosis of lung cancer.

First Report of Penicillium cellarum Causing Rot Disease on Dioscorea polystachya in China.

Dioscorea polystachya (Chinese yam) is a kind of medicine and food homologous crop, the tubers as its main production organ, with high potassium, low fiber, high protein and rich nutrition characteristics. In 2022, at the Chinese herbal medicine planting experimental site in Anguo, Baoding City, Hebei Province, China, we found the symptoms of Chinese yam decay during the storage, with an incidence of 15%~25%. The diseased part of Chinese yam tuber rots expands from the outside to the inside and sags, with a brown or dark brown discoloration, and the surface covered with a thick grayish green mold. The diseased tissue was first rinsed with clean water to remove dirts from the surface. Thereafter, 3 to 4 mm Chinese yam pieces were picked from rotting edge with a sterilized forceps, sterilized with 75% alcohol for 30 s followed by 0.1% mercuric chloride solution for 1min, and then rinsed three times with sterile water. The sterilized pieces were cultured on potato dextrose agar (PDA). One isolated fungus was obtained, and conidia were observed after incubation for 5 days at 26°C. Pure cultures were isolated by single-spore isolation. Conidia were single spore, round or oval, colorless. Conidiophores produce several rounds of symmetric or asymmetric small stems after multiple branches, which were shaped like brooms. The length and width of 100 conidia were measured, and size ranged from 3 to 4×3 to 4 µm. On the basis of morphological characteristics, the isolate was identified as Penicillium spp. (Uy et al. 2022). To further assess the identity of isolated species, the genomic DNA of the fungal isolate (SYRF1) was extracted by CTAB protocol. The ribosomal DNA internal transcribed spacer (ITS) region and the ribosomal large subunit (LSU) were amplified and sequenced with primers ITS1/4, LR5/LROR respectively (White et al. 1990, Xu et al. 2010). The obtained ITS-rDNA region and LSU sequences (GenBank accession OQ707937 and OQ704185) of the isolate were more than 99% identity to the corresponding sequences of Penicillium cellarum in GenBank (KM249068 and MG714818). Phylogenetic results based on a maximum-likelihood analysis revealed that SYRF1 was grouped with P. cellarum. To determine the pathogenicity of the isolated fungi, tests were carried out by aseptic inoculation of fresh and healthy tubers. Before the experiment, the healthy tubers were washed, surface disinfected and dried. The tubers were then wounded with sterile inoculation needles, and the conidium-bearing hyphal discs (5 mm) were inoculated on the surface of the wounded tubers and covered with wet sterile cotton. Three tubers were inoculated repeatedly each time as the experimental group. Inoculate sterile PDA with three tubers as the control group. Each tuber was inoculated with four mycelium disks, and the pathogenicity test was repeated four times. The inoculated tubers were incubated at 26°C for 14 days with sterile PDA as control. After ten days, the inoculated points showed symptoms similar to those of the initial infection, whereas controls remained symptomless. The reisolated fungus matched SYRF1 based on morphological and sequence analyses, thereby fulfilling Koch's postulates. To the best of our knowledge, this is the first report of Penicillium cellarum as causative agent of postharvest rot of Chinese yam tubers in China. This finding will help inform the prevention and management of postharvest diseases of Chinese yam tubers.

Observation of One-Dimensional Dirac Fermions in Silicon Nanoribbons.

Dirac materials, which feature Dirac cones in the reciprocal space, have been one of the hottest topics in condensed matter physics in the past decade. To date, 2D and 3D Dirac Fermions have been extensively studied, while their 1D counterparts are rare. Recently, Si nanoribbons (SiNRs), which are composed of alternating pentagonal Si rings, have attracted intensive attention. However, the electronic structure and topological properties of SiNRs are still elusive. Here, by angle-resolved photoemission spectroscopy, scanning tunneling microscopy/spectroscopy measurements, first-principles calculations, and tight-binding model analysis, we demonstrate the existence of 1D Dirac Fermions in SiNRs. Our theoretical analysis shows that the Dirac cones derive from the armchairlike Si chain in the center of the nanoribbon and can be described by the Su-Schrieffer-Heeger model. These results establish SiNRs as a platform for studying the novel physical properties in 1D Dirac materials.

Observation of Topological Flat Bands in the Kagome Semiconductor Nb3Cl8.

The destructive interference of wavefunctions in a kagome lattice can give rise to topological flat bands (TFBs) with a highly degenerate state of electrons. Recently, TFBs have been observed in several kagome metals, including Fe3Sn2, FeSn, CoSn, and YMn6Sn6. Nonetheless, kagome materials that are both exfoliable and semiconducting are lacking, which seriously hinders their device applications. Herein, we show that Nb3Cl8, which hosts a breathing kagome lattice, is gapped out because of the absence of inversion symmetry, while the TFBs survive because of the protection of the mirror reflection symmetry. By angle-resolved photoemission spectroscopy measurements and first-principles calculations, we directly observe the TFBs and a moderate band gap in Nb3Cl8. By mechanical exfoliation, we successfully obtain monolayer Nb3Cl8, which is stable under ambient conditions. In addition, our calculations show that monolayer Nb3Cl8 has a magnetic ground state, thus providing opportunities to study the interplay among geometry, topology, and magnetism.

Recent Advances in THz Detection of Water.

The frequency range of terahertz waves (THz waves) is between 0.1 and 10 THz and they have properties such as low energy, penetration, transients, and spectral fingerprints, which are especially sensitive to water. Terahertz, as a frontier technology, have great potential in interpreting the structure of water molecules and detecting biological water conditions, and the use of terahertz technology for water detection is currently frontier research, which is of great significance. Firstly, this paper introduces the theory of terahertz technology and summarizes the current terahertz systems used for water detection. Secondly, an overview of theoretical approaches, such as the relaxation model and effective medium theory related to water detection, the relationship between water molecular networks and terahertz spectra, and the research progress of the terahertz detection of water content and water distribution visualization, are elaborated. Finally, the challenge and outlook of applications related to the terahertz wave detection of water are discussed. The purpose of this paper is to explore the research domains on water and its related applications using terahertz technology, as well as provide a reference for innovative applications of terahertz technology in moisture detection.

2 ng/√Hz-resolution optomechanical accelerometer employing a three-dimensional MEMS interferometer.

A portable and high-resolution optomechanical accelerometer employing a deformable grating-based micro-electro-mechanical system (MEMS) interferometer is presented in this Letter. The movable reflective mirror of this interferometer is realized by a low-frequency vertical sensing structure with a three-dimensional (3D)-spring construction, which, to the best of our knowledge, is first proposed and fabricated in this work. All the components of the sensor are packaged in a metal case with a compact size of 4 cm×6 cm×3.15 cm. The micrometer-scale springs permit the device to have a high mechanical sensitivity of 893.23 µm/g and a resultant self-noise below 2 ng/H z from 2 to 7 Hz. Meanwhile, the measured voltage responsivity is as high as 15,874 V/g, demonstrating it is one of the most sensitive accelerometers reported to date.

Topological analysis of the gp41 MPER on lipid bilayers relevant to the metastable HIV-1 envelope prefusion state.

The membrane proximal external region (MPER) of HIV-1 envelope glycoprotein (gp) 41 is an attractive vaccine target for elicitation of broadly neutralizing antibodies (bNAbs) by vaccination. However, current details regarding the quaternary structural organization of the MPER within the native prefusion trimer [(gp120/41)3] are elusive and even contradictory, hindering rational MPER immunogen design. To better understand the structural topology of the MPER on the lipid bilayer, the adjacent transmembrane domain (TMD) was appended (MPER-TMD) and studied. Membrane insertion of the MPER-TMD was sensitive both to the TMD sequence and cytoplasmic residues. Antigen binding of MPER-specific bNAbs, in particular 10E8 and DH511.2_K3, was significantly impacted by the presence of the TMD. Furthermore, MPER-TMD assembly into 10-nm diameter nanodiscs revealed a heterogeneous membrane array comprised largely of monomers and dimers, as enumerated by bNAb Fab binding using single-particle electron microscopy analysis, arguing against preferential trimeric association of native MPER and TMD protein segments. Moreover, introduction of isoleucine mutations in the C-terminal heptad repeat to induce an extended MPER α-helical bundle structure yielded an antigenicity profile of cell surface-arrayed Env variants inconsistent with that found in the native prefusion state. In line with these observations, electron paramagnetic resonance analysis suggested that 10E8 inhibits viral membrane fusion by lifting the MPER N-terminal region out of the viral membrane, mandating the exposure of residues that would be occluded by MPER trimerization. Collectively, our data suggest that the MPER is not a stable trimer, but rather a dynamic segment adapted for structural changes accompanying fusion.