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fig, cells, pubmed, article, mct, mmct, google, scholar, supplementary, mbsg, cell, cas, mmctmbsg, antibody, tumor, cancer, bsg, azd, central, domain, expression, buffer, data, activity, transport, protein, model, structure, lactate, nacl, effab, influx, complex, nature, simulations, extracellular, interactions, mbsgs, analysis, metabolism, antibodies, cryoem, hepes, human, ntd, immunity, nsclcpdos, membrane, mice, fluorescence,

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nature portfolio privacy policy n-acetylglucosaminyl-transferase i-negative outward-open mmct1/mbsg conformation advertising outward-open conformation akin pd-l1/pd-1 blockade therapies n-octyl-β-d-maltopyranoside outward-open mmct1/mbsg triple-negative breast cancer mouse anti-emmprin/cd147 antibody nature 574 nature 591 nature 596 nature mmct4/mbsg-mediated l-lactate influx reprints recent research highlights pharmacological tools targeting guided multi-reference classification model-building tools anti-ig2 polyclonal antibodies i-set immunoglobulin superfamily index primers neuroblastoma-derived exosomes reveal human t-cell ontogeny n-dodecyl-d-maltoside fluorescence-labeled secondary antibodies cryo-em data collection mbsg antibody discovery mmct1/mbsg-mediated pyruvate transport augment anti-tumor immunity yi qin gao single-cell transcriptomics identifies �ferroptosis’-induced cell death analyzing cryo-em data collecting cryo-em data enhancing anti-tumor immunity46 research highlights anti-mouse pd-1 antibody wt mmct1/mbsg/6e7f1fab reconstituted research demonstrated phenix validation tools anti-cancer drug candidates reveal patient-specific vulnerabilities gov/geo/query/acc exploratory research experimental research enhancing anti-tumor immunity fatty acid/lipid pathways

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      headline:A basigin antibody modulates MCTs to impact tumor metabolism and immunity
      description:Lactate metabolism and signaling intricately intertwine in the context of cancer and immunity. Basigin, working alongside monocarboxylate transporters MCT1 and MCT4, orchestrates the movement of lactate across cell membranes. Despite their potential in treating formidable tumors, the mechanisms by which basigin antibodies affect basigin and MCTs remain unclear. Our research demonstrated that basigin positively modulates MCT activity. We subsequently developed a basigin antibody that converts basigin into a negative modulator, thereby suppressing lactate transport and enhancing anti-tumor immunity. Additionally, the antibody alters metabolic profiles in NSCLC-PDOs and T cells. Cryo-EM structural analysis and molecular dynamics simulations reveal that the extracellular Ig2 domain and transmembrane domain of basigin regulate MCT1 activity through an allosteric mechanism. The antibody decreases MCT1 transition rate by reducing the flexibility of basigin’s Ig2 domain and diminishing interactions between basigin’s transmembrane domain and MCT1. These findings underscore the promise of basigin antibodies in combating tumors by modulating metabolism and immunity, and the value of a common therapeutic subunit shared by multiple transporter targets.
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            address:
               name:Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning, China
               type:PostalAddress
            type:Organization
      name:Hong Zhang
      affiliation:
            name:Peking University
            address:
               name:Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, China
               type:PostalAddress
            type:Organization
      name:Xiaofei Zhang
      affiliation:
            name:Fudan University
            address:
               name:Department of Radiation Oncology, Fudan University Shanghai Cancer Center, and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Weixin Zhao
      affiliation:
            name:Fudan University
            address:
               name:Department of Radiation Oncology, Fudan University Shanghai Cancer Center, and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Bin Jia
      affiliation:
            name:Tianjin Cancer Hospital
            address:
               name:Lung Cancer Department, Tianjin Cancer Hospital, Tianjin, China
               type:PostalAddress
            type:Organization
      name:Ningning Li
      url:http://orcid.org/0000-0001-8601-5171
      affiliation:
            name:Peking University
            address:
               name:State Key Laboratory of Membrane Biology, Peking-Tsinghua Joint Center for Life Sciences, School of Life Sciences, Peking University, Beijing, China
               type:PostalAddress
            type:Organization
      name:Ning Gao
      url:http://orcid.org/0000-0003-3067-9993
      affiliation:
            name:Peking University
            address:
               name:State Key Laboratory of Membrane Biology, Peking-Tsinghua Joint Center for Life Sciences, School of Life Sciences, Peking University, Beijing, China
               type:PostalAddress
            type:Organization
      name:Yue Yang
      affiliation:
            name:Lanzhou University
            address:
               name:Institute of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China
               type:PostalAddress
            type:Organization
      name:Dongxi Xiang
      affiliation:
            name:the Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine
            address:
               name:State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, and Department of Biliary-Pancreatic Surgery, the Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Shan Wang
      affiliation:
            name:Guangxi Medical University Cancer Hospital
            address:
               name:Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Yi Qin Gao
      affiliation:
            name:Peking University
            address:
               name:Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Jun Liao
      url:http://orcid.org/0000-0001-7487-5545
      affiliation:
            name:ShanghaiTech University
            address:
               name:School of Life Science and Technology, ShanghaiTech University, Shanghai, China
               type:PostalAddress
            type:Organization
            name:Foshan
            address:
               name:Alphelix Biosciences, Foshan, Guangdong, China
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:School of Life Science and Technology, ShanghaiTech University, Shanghai, China
      name:School of Life Science and Technology, ShanghaiTech University, Shanghai, China
      name:Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, China
      name:Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning, China
      name:Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning, China
      name:Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning, China
      name:Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, China
      name:Department of Radiation Oncology, Fudan University Shanghai Cancer Center, and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
      name:Department of Radiation Oncology, Fudan University Shanghai Cancer Center, and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
      name:Lung Cancer Department, Tianjin Cancer Hospital, Tianjin, China
      name:State Key Laboratory of Membrane Biology, Peking-Tsinghua Joint Center for Life Sciences, School of Life Sciences, Peking University, Beijing, China
      name:State Key Laboratory of Membrane Biology, Peking-Tsinghua Joint Center for Life Sciences, School of Life Sciences, Peking University, Beijing, China
      name:Institute of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China
      name:State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, and Department of Biliary-Pancreatic Surgery, the Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
      name:Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning, China
      name:Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, China
      name:School of Life Science and Technology, ShanghaiTech University, Shanghai, China
      name:Alphelix Biosciences, Foshan, Guangdong, China

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