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Structure and receptor-binding properties of an airborne transmissible avian infl uenza A virus hemagglutinin H5(VN1203mut)

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Protein & Cell 2013年第7期4卷 502-511页

作者： Xishan Lu Yi Shi Wei Zhang Yanfang Zhang Jianxun Qi George F Gao College of Veterinary Medicine China Agricultural UniversityBeijing 100193China Research Network of Immunity and Health(RNIH) Beijing Institutes of Life ScienceChinese Academy of SciencesBeijing 100101China CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Chinese Academy of SciencesBeijing 100049China Laboratory of Protein Engineering and Vaccines Tianjin Institute of Industrial BiotechnologyChinese Academy of SciencesTianjin 300308China National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and Prevention(China CDC)Beijing 102206China

Avian infl uenza A virus continues to pose a global threat with occasional H5N1 human infections,which is em-phasized by a recent severe human infection caused by avian-origin H7N9 in *** these viruses do not transmit effi ciently in human *** a few ami-no acid substitutions of the hemagglutinin H5 protein in the laboratory,two H5 mutants have been shown to obtain an air-borne transmission in a mammalian ferret *** in this study one of the mutant H5 proteins devel-oped by Kawaoka’s group(VN1203mut)was expressed in a baculovirus system and its receptor-binding properties were *** herein show that the VN1203mut had a dramatically reduced binding affi nity for the avianα2,3-linkage receptor compared to wild type but showed no detectable increase in affi nity for the humanα2,6-linkage receptor,using Surface Plasmon Resonance ***,the crystal structures of the VN1203mut and its complexes with either human or avian receptors demon-strate that the VN1203mut binds the human receptor in the same binding manner(cis conformation)as seen for the HAs of previously reported 1957 and 1968 pandemic influenza *** receptor binding and crystallo-graphic data shown here further confi rm that the ability to bind the avian receptor has to decrease for a higher hu-man receptor binding affi *** the Q226L substitution is shown important for obtaining human receptor binding,we suspect that the newly emerged H7N9 binds human receptor as H7 has a Q226L substitution.

关键词： airborne transmission H5 avian infl uenza structure receptor binding

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Insulin: a small protein with a long journey

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Protein & Cell 2010年第6期1卷 537-551页

作者： Qingxin Hua Department of Biochemistry Case Western Reserve UniversityClevelandOhio 44106-4935USA

Insulin is a hormone that is essential for regulating energy storage and glucose metabolism in the *** in liver,muscle,and fat tissues stimulates the cell to take up glucose from blood and store it as glycogen in liver and *** of insulin control causes diabetes mellitus(DM).Insulin is the unique medicine to treat some forms of *** population of diabetics has dramatically increased over the past two decades,due to high absorption of carbohydrates(or fats and proteins),lack of physical exercise,and development of new diagnostic *** present,the two largest developing countries(India and China)and the largest developed country(United States)represent the top three countries in terms of diabetic *** is a small protein,but contains almost all structural features typical of proteins:α-helix,β-sheet,β-turn,high order assembly,allosteric T→R-transition,and conformational changes in amyloidal *** than ten years’efforts on studying insulin disulfide intermediates by NMR have enabled us to decipher the whole picture of insulin folding coupled to disulfide pairing,especially at the initial stage that forms the nascent *** structural switches are also known to regulate insulin binding to receptors and progress has been made to identify the residues involved in ***,resolving the complex structure of insulin and its receptor remains a challenge in insulin ***,the accumulated knowledge of insulin structure has allowed us to specifically design a new ultra-stable and active single-chain insulin analog(SCI-57),and provides a novel way to design super-stable,fast-acting and cheaper insulin formulations for DM *** this long journey of insulin study will benefit basic research in proteins and in pharmaceutical therapy.

关键词： insulin diabetes receptor binding folding disulfide pairing NMR

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Emergence of a novel reassortant avian influenza virus(H10N3) in Eastern China with high pathogenicity and respiratory droplet transmissibility to mammals

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Science China(Life Sciences) 2022年第5期65卷 1024-1035页

作者： Kaituo Liu Pingyun Ding Yuru Pei Ruyi Gao Wenwen Han Huafen Zheng Zhuxing Ji Miao Cai Jinyuan Gu Xiuli Li Min Gu Jiao Hu Xiaowen Liu Shunlin Hu Pinghu Zhang Xiaobo Wang Xiaoquan Wang Xiufan Liu College of Veterinary Medicine Yangzhou UniversityYangzhou 225009China Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis Yangzhou UniversityYangzhou 225009China Jiangsu Key Laboratory of Zoonosis Yangzhou 225009China Institute of Translational Medicine Key Laboratory of Geriatric Disease Prevention and Control of Jiangsu ProvinceMedical CollegeYangzhou UniversityYangzhou 225009China

Decades have passed since the first discovery of H10-subtype avian influenza virus(AIV) in chickens in 1949,and it has been detected in many species including mammals such as minks,pigs,seals and *** of human infections with H10N8viruses identified in China in 2013 have raised widespread *** novel reassortant H10N3 viruses were isolated from chickens in December 2019 in eastern China during routine surveillance for *** internal genes of these viruses were derived from genotype S(G57) H9N2 and were consistent with H5N6,H7N9 and H10N8,which cause fatal infections in *** viral pathogenicity and transmissibility were further studied in different animal *** two H10N3 isolates had low pathogenicity in chickens and were transmitted between chickens via direct *** viruses were highly pathogenic in mice and could be transmitted between guinea pigs via direct contact and respiratory *** importantly,these viruses can bind to both human-type SAα-2,6-Gal receptors and avian-type SAα-2,3-Gal *** shedding in chickens and good adaptability to mammals of these H10N3 isolates would make it easier to transmit to humans and pose a threat to public health.

关键词： H10N3 H9N2 receptor binding pathogenicity respiratory droplet transmissibility

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The relationship between the connecting peptide of recombined single chain insulin and its biological function

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Science China(Life Sciences) 2001年第6期44卷 593-600页

作者：黄一丁梁镇和冯佑民 State Key Laboratory of Molecular Biology Shanghai Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China

To investigate the relationship between the biological activity of recombined single chain insulin and the length of the connecting peptide, we designed and prepared three single chain insulin molecules, namely, PIP, [A]5PIP and [A]10PIP, by site-directed mutagenesis, in which B30 and A1 were linked through dipeptide A-K, heptapeptide A-A-A-A-A-A-K, and dodecapeptide A-A-A-A-A-A-A-A-A-A-A-K, respectively. Their receptor binding capacities were 0.14%, 14.3% and 11.1% of that of insulin respectively and their in vivo biological activities were in consistence with their receptor binding capacity; whereas their growth promoting activities were 17%, 116.3% and 38% of that of insulin. These results suggested the following conclusions. (i) The recombined single chain insulin could also possess the same metabolic and mitogenic function as insulin. (ii) The receptor binding capacity of recombined single chain insulin to insulin receptor was closely related to the length and amino acid composition of the connecting peptide and could change from 0 to 100% of insulin depending on the different connecting peptides. This result further illustrated the necessity of B chain C-terminus swaying away from A chain N-terminus when insulin binds to its receptor. (iii) The mitogenic activity of recombined single chain insulin also depended on the length and the amino acid composition of the connecting peptide and was higher than its metabolic activity.

关键词： insulin single chain insulin receptor binding growth promoting GR2H6 cell line.

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Enzymatic Semi-synthesis and Properties of Chimeric Molecule "Epidermal Growth Factor-insulin Fragment"

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Progress in Natural Science:Materials International 1993年第5期 440-446页

作者：严民宏冯佑民张友尚 PRC Shanghai 200031 Shanghai Institute of Biochemistry Academia Sinica State Key Laboratory of Laser Technology Huazhong University of Science and Technology.Wuhan 430074 State Key Laboratory of Molecular Biology

By means of enzymatic *** molecules mEGF-GFFNH2andDPmEGF-GFFNH2were obtained from mEGF, DPmEGF and GFFNH2,Their mitogenic activities andEGF receptor binding capacities were *** insulin receptor binding capacity of mEGF-GFFNH2was also *** results indicate that mEGF-GFFNH2and DPmEGF-GFFNH2almost have the samemitogenic and receptor binding potency as those of mEGF and *** Chimeric moleculemEGF-GFFNH2,at high concentration can also bind specifically with insulin receptor.

关键词： epidermal growth factor insulin chimeric molecule mitogenic activity receptor binding

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The Role of Hemagglutinin-esterase-fusion Glycoprotein from Newly-identified Influenza D Virus in Viral Entry

The Role of Hemagglutinin-esterase-fusion Glycoprotein from ...

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第十一届全国免疫学学术大会

作者： Song Hao Qi Jianxun Varki Ajit Shi Yi Gao George F Research Network of Immunity and Health (RNIH) Beijing Institutes of Life ScienceChinese Academy of Sciences CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of Sciences University of California

Background:Of the Orthomyxoviridae family of viruses,influenza A,B and C viruses all can cause disease in ***,a novel influenza D virus(IDV) with approximately 50% amino acid identity to human influenza C virus(ICV) is found in pigs and *** novel virus has a broader cell tropism than human ICV and is capable of infecting ferrets,pigs and guinea pigs and transmit to naive animals by direct ***:To investigate the cellular receptor for viral entry and the molecular mechanism for its broad host ***:We determined the receptor of IDV by glycan microarray analysis,and determined the crystal structures of hemagglutinin-esterase-fusion glycoprotein(HEF) of IDV,both in its free form and in complex with the receptor and enzymatic substrate ***:We demonstrated that IDV(like ICV) uses 9-O-acetylated sialic acid as its receptor,but the IDV HEF has an open receptor-binding cavity to accommodate diverse extended glycan *** structural difference provides an explanation for the phenomenon that the IDV has a broad cell ***:Our findings reveal in exquisite detail how the receptors or substrates bind to the receptor-binding site or esterase active site,providing a clue for the development of novel therapeutics against the conserved esterase ***,the IDV HEF can bind human trachea epithelia,indicating that the IDV virus may become a potential threat to public health.

关键词： crystal structure HEF influenza D virus receptor binding viral entry

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