Communications Biology最新文献_第3页

Single-cell transcriptomic profiling reveals cell type heterogeneity between HFpEF and HFrEF. 单细胞转录组分析揭示了HFpEF和HFrEF之间的细胞类型异质性。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-10-07 DOI: 10.1038/s42003-025-08827-w

Xingqi Xiao, Wenqian Wu, Qilong Mao, Bolun Li, Jixin Wang, Sheng Liu, Hongmei Zhao, Erping Long, Jing Wang

{"title":"Single-cell transcriptomic profiling reveals cell type heterogeneity between HFpEF and HFrEF.","authors":"Xingqi Xiao, Wenqian Wu, Qilong Mao, Bolun Li, Jixin Wang, Sheng Liu, Hongmei Zhao, Erping Long, Jing Wang","doi":"10.1038/s42003-025-08827-w","DOIUrl":"10.1038/s42003-025-08827-w","url":null,"abstract":"Heart failure with preserved ejection fraction (HFpEF) as a high heterogeneity clinical syndrome, is commonly associated with diastolic dysfunction, and has no effective therapy, which is obviously distinct from Heart failure with reduced ejection fraction (HFrEF). Currently the differences of cell type heterogeneity between HFpEF and HFrEF remain largely unknown. Here we illustrate an atlas consisting of 21,747 cardiac cells, including both HFpEF and HFrEF. Cell-cell communication analysis reveals cardiomyocytes rather than endothelium or fibroblasts were dominant communication \"hub\" in HFpEF. The subtypes of cardiomyocytes are highly heterogeneous between HFpEF and HFrEF. Notably, a specific subtype of cardiomyocytes shows significant gene expression associated with the metabolism of fatty acids. Additionally, regulon analysis reveals that Ppargc1a, Atf6, E2f6, and Mitf exhibited specific elevated regulation in the subtype of cardiomyocytes of HFpEF. Furthermore, we have identified 210 HF susceptibility genes from HF-associated GWAS data. After integrating scRNA-seq, GWAS, and eQTL data, the genetic susceptibility underlying HFpEF and HFrEF were discussed. In conclusion, this study not only comprehensively characterizes the differences of cardiomyocytes changes but also provides insights into potential targets for cell type- and subtype-specific molecules between HFpEF and HFrEF.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1436"},"PeriodicalIF":5.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12504458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NAA60 facilitates LRRC8A- and LRRC8D-mediated platinum drug uptake. NAA60促进LRRC8A-和lrrc8d介导的铂类药物摄取。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-10-06 DOI: 10.1038/s42003-025-08826-x

Carmen Alexandra Widmer, Anna Moyseos, Ismar Klebic, Martina Dettwiler, Martín González-Fernández, Ewa Gogola, Myriam Siffert, Natasha Buchs, Sophie Braga-Lagache, Anne-Christine Uldry, Jos Jonkers, Manfred Heller, Sven Rottenberg

{"title":"NAA60 facilitates LRRC8A- and LRRC8D-mediated platinum drug uptake.","authors":"Carmen Alexandra Widmer, Anna Moyseos, Ismar Klebic, Martina Dettwiler, Martín González-Fernández, Ewa Gogola, Myriam Siffert, Natasha Buchs, Sophie Braga-Lagache, Anne-Christine Uldry, Jos Jonkers, Manfred Heller, Sven Rottenberg","doi":"10.1038/s42003-025-08826-x","DOIUrl":"10.1038/s42003-025-08826-x","url":null,"abstract":"The platinum-based drugs cis- and carboplatin, which are crucial for treating cancers with DNA repair defects, like those caused by BRCA1/2 mutations, rely on the volume-regulated anion channel subunits LRRC8A and LRRC8D for about 50% of cellular drug uptake. Yet, the precise mechanisms of how LRRC8A and LRRC8D mediate this function are largely unknown. Here, we identify NAA60, an N-terminal acetyltransferase, which localizes to the Golgi apparatus to affect LRRC8A and LRRC8D function. Our data suggest that NAA60 acetylates the LRRC8A/D N-termini, and its loss decreases cis- and carboplatin uptake resulting in drug resistance of otherwise hypersensitive BRCA1;p53-deficient cells and tumors. Furthermore, we mimicked the absence of the neutralizing acetyl moiety that is observed after loss of NAA60 by introducing positively charged amino acids at the N-termini of LRRC8A/D, which indeed decreased cis- and carboplatin sensitivity. Our findings highlight the importance of N-terminal acetylation by NAA60 for effective platinum drug uptake, offering new insights into overcoming drug resistance.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1431"},"PeriodicalIF":5.1,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel regulators of heparan sulfate proteoglycans modulate cellular uptake of α-synuclein fibrils. 硫酸肝素蛋白聚糖的新调节剂调节α-突触核蛋白原纤维的细胞摄取。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-10-06 DOI: 10.1038/s42003-025-08786-2

Benoît Vanderperre, Amitha Muraleedharan, Marie-France Dorion, Frédérique Larroquette, Esther Del Cid Pellitero, Nishani Rajakulendran, Carol X-Q Chen, Roxanne Larivière, Charlotte Michaud-Tardif, Thomas Goiran, Rony Chidiac, Damien Lipuma, Graham MacLeod, Rhalena Thomas, Zhangjie Wang, Wolfgang E Reintsch, Wen Luo, Irina Shlaifer, Fuming Zhang, Ke Xia, Zachary Steinhart, Robert J Linhardt, Jean-François Trempe, Jian Liu, Thomas M Durcan, Stephane Angers, Edward A Fon

{"title":"Novel regulators of heparan sulfate proteoglycans modulate cellular uptake of α-synuclein fibrils.","authors":"Benoît Vanderperre, Amitha Muraleedharan, Marie-France Dorion, Frédérique Larroquette, Esther Del Cid Pellitero, Nishani Rajakulendran, Carol X-Q Chen, Roxanne Larivière, Charlotte Michaud-Tardif, Thomas Goiran, Rony Chidiac, Damien Lipuma, Graham MacLeod, Rhalena Thomas, Zhangjie Wang, Wolfgang E Reintsch, Wen Luo, Irina Shlaifer, Fuming Zhang, Ke Xia, Zachary Steinhart, Robert J Linhardt, Jean-François Trempe, Jian Liu, Thomas M Durcan, Stephane Angers, Edward A Fon","doi":"10.1038/s42003-025-08786-2","DOIUrl":"10.1038/s42003-025-08786-2","url":null,"abstract":"Synucleinopathies are characterized by the accumulation and propagation of α-synuclein (α-syn) aggregates throughout the brain, leading to neuronal dysfunction and death. In this study, we used an unbiased FACS-based genome-wide CRISPR/Cas9 knockout screening to identify genes that regulate the entry and accumulation of α-syn preformed fibrils (PFFs) in cells. We identified key genes and pathways specifically implicated in α-syn PFFs intracellular accumulation, including heparan sulfate proteoglycans (HSPG) biosynthesis and Golgi trafficking. All confirmed hits affected heparan sulfate (HS), a post-translational modification known to act as a receptor for proteinaceous aggregates including α-syn and tau. Intriguingly, deletion of SLC39A9 and C3orf58 genes, encoding respectively a Golgi-localized exporter of Zn2+, and the Golgi-localized putative kinase DIPK2A, specifically impaired the uptake of α-syn PFFs, by preventing the binding of PFFs to the cell surface. Mass spectrometry-based analysis of HS chains in SLC39A9-/- and C3orf58-/- cells indicated major defects in HS homeostasis. Additionally, Golgi accumulation of NDST1, a prime HSPG biosynthetic enzyme, was detected in C3orf58-/- cells. Interestingly, C3orf58-/- human iPSC-derived microglia and dopaminergic neurons exhibited a strong reduction in their ability to internalize α-syn PFFs. Altogether, our data identifies new modulators of HSPGs that regulate α-syn PFFs cell surface binding and uptake.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1426"},"PeriodicalIF":5.1,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A conserved mechanism of LRRC8 channel inhibition by two structurally distinct drugs. 两种结构不同的药物抑制LRRC8通道的保守机制。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-10-06 DOI: 10.1038/s42003-025-08795-1

Toshiki Yamada, Paola Bisignano, Erkan Karakas, Jerod S Denton

{"title":"A conserved mechanism of LRRC8 channel inhibition by two structurally distinct drugs.","authors":"Toshiki Yamada, Paola Bisignano, Erkan Karakas, Jerod S Denton","doi":"10.1038/s42003-025-08795-1","DOIUrl":"10.1038/s42003-025-08795-1","url":null,"abstract":"Leucine Rich Repeat Containing 8 (LRRC8) anion channels are emerging therapeutic targets, but their pharmacology is poorly developed. We employed a structurally defined homomeric channel chimera (8C-8A(IL125)) and heteromeric LRRC8A/LRRC8C (8A/8C) channels to investigate the mechanism of action of two structurally distinct LRRC8 inhibitors: zafirlukast and pranlukast. Molecular dynamics simulations identified zafirlukast binding sites in 8C-8A(IL125) comprising the amino (N)-terminal domain (NTD) and inter-subunit fenestrae between transmembrane (TM) helices 1 and 2. Pranlukast also clusters in fenestrae albeit closer to the external pore. Patch clamp analysis revealed that mutations in NTD, TM1, and TM2 alter 8C-8A(IL125) and 8A/8C sensitivity to zafirlukast and pranlukast, suggesting a common mechanism. The association between voltage-dependent inactivation induced by mutations or low pH and inhibitor sensitivity suggests that drug inhibition involves disruption of protein-lipid interactions and destabilization of the pore. This may represent a common mechanism of LRRC8 channel inhibition by lipophilic drugs.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1432"},"PeriodicalIF":5.1,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hypomethylation of thrombospondin-1 promoter region is associated with reduced aqueous humor flow. 血小板反应蛋白-1启动子区域的低甲基化与房水流量减少有关。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-10-06 DOI: 10.1038/s42003-025-08833-y

Kit Ying Choy, Wei-Ying Yang, Choi-Ying Ling, King-Kit Li, Hoi Lam Li, Hong-Lok Lung, Chi-Ho To, Chi Wai Do, W Daniel Stamer, Samantha Sze-Wan Shan

{"title":"Hypomethylation of thrombospondin-1 promoter region is associated with reduced aqueous humor flow.","authors":"Kit Ying Choy, Wei-Ying Yang, Choi-Ying Ling, King-Kit Li, Hoi Lam Li, Hong-Lok Lung, Chi-Ho To, Chi Wai Do, W Daniel Stamer, Samantha Sze-Wan Shan","doi":"10.1038/s42003-025-08833-y","DOIUrl":"10.1038/s42003-025-08833-y","url":null,"abstract":"Prolonged use of dexamethasone (DEX) elevates intraocular pressure (IOP) and increases the risk of developing glaucoma. In a previous study, we demonstrate that DEX stimulates the expression of thrombospondin-1 (THBS1) in primary human trabecular meshwork (hTM) cells, and that inhibiting THBS1 expression prevents DEX-induced elevation of IOP in mice. Therefore, we investigate the mechanism by which DEX regulates THBS1 expression. Treatment with the DNA methylation inhibitors, 5-azacytosine (5-AC) or 5-aza-2'-deoxycytidine (5-aza-dC), upregulates THBS1 protein levels in vitro and in vivo, reduces outflow facility in perfused mouse eyes, and elevates IOP in mice. In primary hTM cells, 7-day DEX treatment results in hypomethylation of the THBS1 promoter region and reduces transcript levels of 2 DNA methyltransferases (DNMTs), DNMT1 and DNMT3A. Taken together, we show that DEX reduces expression of DNMTs and DNA methylation of the THBS1 promoter region, supporting a critical role for THBS1 in DEX-induced outflow reduction.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1430"},"PeriodicalIF":5.1,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of an ultrahigh affinity, trimeric ACE2 biologic as a universal SARS-CoV-2 antagonist. 开发一种具有超高亲和力的三聚体ACE2生物制剂作为通用的SARS-CoV-2拮抗剂。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-10-06 DOI: 10.1038/s42003-025-08819-w

Juliet Gonzales, Tynan Young, Hyeran Choi, Miso Park, Yead Jewel, Chengcheng Fan, Rahul Purohit, Pamela J Bjorkman, John C Williams

{"title":"Development of an ultrahigh affinity, trimeric ACE2 biologic as a universal SARS-CoV-2 antagonist.","authors":"Juliet Gonzales, Tynan Young, Hyeran Choi, Miso Park, Yead Jewel, Chengcheng Fan, Rahul Purohit, Pamela J Bjorkman, John C Williams","doi":"10.1038/s42003-025-08819-w","DOIUrl":"10.1038/s42003-025-08819-w","url":null,"abstract":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, utilizes membrane-bound, angiotensin-converting enzyme II (ACE2) for internalization and infection. We describe the development of a biologic that takes advantage of the proximity of the N-terminus of bound ACE2 to the three-fold symmetry axis of the spike protein to create an ultrapotent, trivalent ACE2 entry antagonist. Distinct disulfide bonds were added to enhance serum stability and a single point mutation was introduced to eliminate enzymatic activity. Through surface plasmon resonance, pseudovirus neutralization assays, and single-particle cryo-electron microscopy, we show this antagonist binds to and inhibits SARS-CoV-2 variants. We further show the antagonist binds to and inhibits a 2003 SARS-CoV-1 strain. Collectively, structural insight has allowed us to design a universal trivalent antagonist against all variants of SARS-CoV-2 tested, suggesting it will be active against the emergence of future mutants.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1428"},"PeriodicalIF":5.1,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cryo-EM structure of phospholipase Cε defines N-terminal domains and their roles in activity. 磷脂酶Cε的低温电镜结构定义了n端结构域及其在活性中的作用。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-10-06 DOI: 10.1038/s42003-025-08831-0

Kadidia Samassekou, Elisabeth E Garland-Kuntz, Vaani Ohri, Isaac J Fisher, Satchal K Erramilli, Kaushik Muralidharan, Livia M Bogdan, Abigail M Gick, Anthony Kossiakoff, Angeline M Lyon

{"title":"Cryo-EM structure of phospholipase Cε defines N-terminal domains and their roles in activity.","authors":"Kadidia Samassekou, Elisabeth E Garland-Kuntz, Vaani Ohri, Isaac J Fisher, Satchal K Erramilli, Kaushik Muralidharan, Livia M Bogdan, Abigail M Gick, Anthony Kossiakoff, Angeline M Lyon","doi":"10.1038/s42003-025-08831-0","DOIUrl":"10.1038/s42003-025-08831-0","url":null,"abstract":"Phospholipase Cε (PLCε) increases intracellular Ca2+ and protein kinase C (PKC) activity in the cardiovascular system in response to stimulation of G protein coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs). The ability of PLCε to respond to these diverse inputs is due, in part, to multiple, conformationally dynamic regulatory domains. However, this heterogeneity has limited structural studies of the lipase to either individual domains or its catalytic core. Here, we report the 3.9 Å reconstruction of the largest fragment of PLCε to date in complex with an antigen binding fragment (Fab). The structure reveals that PLCε contains a pleckstrin homology (PH) domain and four tandem EF hands, including subfamily-specific insertions and intramolecular interactions with the catalytic core. The structure, together with a model of the holoenzyme, suggest that part of the N-terminus and PH domain may form a surface that supports lipase activity. Functional characterization of this surface confirms it is critical for maximum basal and G protein-stimulated activities. This study provides new insights into the autoinhibited, basal conformation of PLCε and how the N-terminal domains contribute to activity.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1429"},"PeriodicalIF":5.1,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The acetyltransferase CysE modulates virulence and drug resistance of Mycobacterium tuberculosis by interfering with oxidative stress responses. 乙酰转移酶CysE通过干扰氧化应激反应调节结核分枝杆菌的毒力和耐药性。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-10-06 DOI: 10.1038/s42003-025-08670-z

Lan-Yue Zhang, Han Yin, Ying-Chao Wang, Mei-Yi Yan, Chun-Liang Wang, Xue-Tian Shang, Wei-Yi Liu, Zi-Hui Li, Hong-Yan Jia, Zong-De Zhang, Chuan-Zhi Zhu, Li-Ping Pan, Yi-Cheng Sun

{"title":"The acetyltransferase CysE modulates virulence and drug resistance of Mycobacterium tuberculosis by interfering with oxidative stress responses.","authors":"Lan-Yue Zhang, Han Yin, Ying-Chao Wang, Mei-Yi Yan, Chun-Liang Wang, Xue-Tian Shang, Wei-Yi Liu, Zi-Hui Li, Hong-Yan Jia, Zong-De Zhang, Chuan-Zhi Zhu, Li-Ping Pan, Yi-Cheng Sun","doi":"10.1038/s42003-025-08670-z","DOIUrl":"10.1038/s42003-025-08670-z","url":null,"abstract":"Acetyltransferases play a crucial role in biological processes by modifying a variety of substrates. However, their roles in the virulence of Mycobacterium tuberculosis (M. tb) are poorly understood. To systematically investigate the roles of acetyltransferases in M. tb, we constructed an acetyltransferase mutant library using CRISPR-assisted genome editing and screened for genes that are essential for mouse infection. Seven acetyltransferases were identified as essential for lung infection of M. tb. cysE, encoding a serine acetyltransferase, was confirmed to be required for virulence of M. tb in mice and its replication in macrophages. Further experiments revealed that mutation of cysE or inhibition of CysE by small molecular chemical increased sensitivity to clofazimine treatment. Finally, we demonstrated that cysE is involved in mitigating oxidative stress, which modulates the virulence and drug resistance of M. tb. Our study suggests that targeting cysE offers potential for the development of anti-tuberculosis drugs, particularly for enhancing treatment regimens for drug-resistant tuberculosis through the synergistic effect with clofazimine.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1425"},"PeriodicalIF":5.1,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structure and function of a cross-neutralizing influenza neuraminidase antibody that accommodates recent N2 NA Asn245 glycosylation. 交叉中和流感神经氨酸酶抗体的结构和功能，适应最近的N2 NA Asn245糖基化。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-10-06 DOI: 10.1038/s42003-025-08830-1

Xueyong Zhu, Ahmed M Khalil, Michael S Piepenbrink, Wenli Yu, Yao Ma, Luis Martinez-Sobrido, Ian A Wilson, James J Kobie

{"title":"Structure and function of a cross-neutralizing influenza neuraminidase antibody that accommodates recent N2 NA Asn245 glycosylation.","authors":"Xueyong Zhu, Ahmed M Khalil, Michael S Piepenbrink, Wenli Yu, Yao Ma, Luis Martinez-Sobrido, Ian A Wilson, James J Kobie","doi":"10.1038/s42003-025-08830-1","DOIUrl":"10.1038/s42003-025-08830-1","url":null,"abstract":"Monoclonal antibodies (mAbs) that recognize and inhibit a diverse range of influenza viruses, although relatively rare, have been isolated following infection or vaccination. Study of their ontology and mechanisms of action informs universal vaccine and therapeutic development. We have previously described a potent and broad neuraminidase (NA)-neutralizing human mAb, 1122A11, that neutralizes a wide range of H3N2 viruses. Here, further characterization of 1122A11 reveals reactivity to cross-group influenza A virus NAs, including group-1 N1 and N8, and group-2 N2 and N3 NAs. Recent H3N2 viruses have acquired Asn245 glycosylation on the active site rim. Crystal structures of an N2 NA from A/Singapore/INFIMH-16-0019/2016 (H3N2) at 2.3 Å (apo) and 2.2 Å (Fab bound) resolution showed that 1122A11 binding causes local changes to the periphery of NA active site to accommodate the glycan. The CDRH3 of 1122A11 inserts into the active site and mimics the substrate sialic acid. We then determined that the ability of 1122A11 to protect from lethal challenge in mice is not dependent on Fc-effector function. These results highlight the therapeutic potential of 1122A11 as a broad protective anti-viral and reinforce pursuit of immunogen development of NA antibodies toward achieving more universal influenza protection.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1427"},"PeriodicalIF":5.1,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Author Correction: HMGB2-induced calreticulin translocation required for immunogenic cell death and ferroptosis of cancer cells are controlled by the nuclear exporter XPO1. 作者更正：hmgb2诱导的钙调钙蛋白易位是免疫原性细胞死亡和癌细胞铁凋亡所必需的，是由核出口蛋白XPO1控制的。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-10-04 DOI: 10.1038/s42003-025-08894-z

Jingqi Fan, Kevin P Gillespie, Clementina Mesaros, Ian A Blair

引用次数: 0