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Adrianna P. P. Zhang Zachary A. Bornholdt Dafna M. Abelson Erica Ollmann Saphire 《Journal of virology》2014,88(10):5859-5863
The VP24 protein plays an essential, albeit poorly understood role in the filovirus life cycle. VP24 is only 30% identical between Marburg virus and the ebolaviruses. Furthermore, VP24 from the ebolaviruses is immunosuppressive, while that of Marburg virus is not. The crystal structure of Marburg virus VP24, presented here, reveals that although the core is similar between the viral genera, Marburg VP24 is distinguished by a projecting β-shelf and an alternate conformation of the N-terminal polypeptide. 相似文献
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Jessica F. Bruhn Katherine C. Barnett Jaclyn Bibby Jens M. H. Thomas Ronan M. Keegan Daniel J. Rigden Zachary A. Bornholdt Erica Ollmann Saphire 《Journal of virology》2014,88(1):758-762
The Nipah virus phosphoprotein (P) is multimeric and tethers the viral polymerase to the nucleocapsid. We present the crystal structure of the multimerization domain of Nipah virus P: a long, parallel, tetrameric, coiled coil with a small, α-helical cap structure. Across the paramyxoviruses, these domains share little sequence identity yet are similar in length and structural organization, suggesting a common requirement for scaffolding or spatial organization of the functions of P in the virus life cycle. 相似文献
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Lee JE Kuehne A Abelson DM Fusco ML Hart MK Saphire EO 《Journal of molecular biology》2008,375(1):202-216
13F6-1-2 is a murine monoclonal antibody that recognizes the heavily glycosylated mucin-like domain of the Ebola virus virion-attached glycoprotein (GP) and protects animals against lethal viral challenge. Here we present the crystal structure, at 2.0 Å, of 13F6-1-2 in complex with its Ebola virus GP peptide epitope. The GP peptide binds in an extended conformation, anchored primarily by interactions with the heavy chain. Two GP residues, Gln P406 and Arg P409, make extensive side-chain hydrogen bond and electrostatic interactions with the antibody and are likely critical for recognition and affinity. The 13F6-1-2 antibody utilizes a rare Vλx light chain. The three light-chain complementarity-determining regions do not adopt canonical conformations and represent new classes of structures distinct from Vκ and other Vλ light chains. In addition, although Vλx had been thought to confer specificity, all light-chain contacts are mediated through germ-line-encoded residues. This structure of an antibody that protects against the Ebola virus now provides a framework for humanization and development of a postexposure immunotherapeutic. 相似文献
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Syndecans serve as attachment receptors for human immunodeficiency virus type 1 on macrophages 下载免费PDF全文
Macrophages are thought to represent one of the first cell types in the body to be infected during the early stage of human immunodeficiency virus type 1 (HIV-1) transmission and represent a potential viral reservoir in vivo. Thus, an understanding of HIV-1 attachment to these cells is fundamental to the development of novel anti-HIV-1 therapies. Although one of the major targets of HIV-1 in vivo--CD4(+) T lymphocytes--express high CD4 levels, other major targets such as macrophages do not. We asked in this study whether this low CD4 level on macrophages is sufficient to support HIV-1 attachment to these cells or whether cell surface proteins other than CD4 are required for this process. We show that CD4 alone is not sufficient to support the initial adsorption of HIV-1 to macrophages. Importantly, we find that heparan sulfate proteoglycans (HSPGs) serve as the main class of attachment receptors for HIV-1 on macrophages. Most importantly, we demonstrate that a single family of HSPGs, the syndecans, efficiently mediates HIV-1 attachment and represents an abundant class of attachment receptors on macrophages. 相似文献
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Frederick W. Holtsberg Sergey Shulenin Hong Vu Katie A. Howell Sonal J. Patel Bronwyn Gunn Marcus Karim Jonathan R. Lai Julia C. Frei Elisabeth K. Nyakatura Larry Zeitlin Robin Douglas Marnie L. Fusco Jeffrey W. Froude Erica Ollmann Saphire Andrew S. Herbert Ariel S. Wirchnianski Calli M. Lear-Rooney Galit Alter John M. Dye Pamela J. Glass Kelly L. Warfield M. Javad Aman 《Journal of virology》2016,90(1):266-278
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Marnie L. Fusco Takao Hashiguchi Robyn Cassan Julia E. Biggins Charles D. Murin Kelly L. Warfield Sheng Li Frederick W. Holtsberg Sergey Shulenin Hong Vu Gene G. Olinger Do H. Kim Kevin J. Whaley Larry Zeitlin Andrew B. Ward Cory Nykiforuk M. Javad Aman Jody Berry Erica Ollmann Saphire 《PLoS pathogens》2015,11(6)
The filoviruses, which include the marburg- and ebolaviruses, have caused multiple outbreaks among humans this decade. Antibodies against the filovirus surface glycoprotein (GP) have been shown to provide life-saving therapy in nonhuman primates, but such antibodies are generally virus-specific. Many monoclonal antibodies (mAbs) have been described against Ebola virus. In contrast, relatively few have been described against Marburg virus. Here we present ten mAbs elicited by immunization of mice using recombinant mucin-deleted GPs from different Marburg virus (MARV) strains. Surprisingly, two of the mAbs raised against MARV GP also cross-react with the mucin-deleted GP cores of all tested ebolaviruses (Ebola, Sudan, Bundibugyo, Reston), but these epitopes are masked differently by the mucin-like domains themselves. The most efficacious mAbs in this panel were found to recognize a novel “wing” feature on the GP2 subunit that is unique to Marburg and does not exist in Ebola. Two of these anti-wing antibodies confer 90 and 100% protection, respectively, one hour post-exposure in mice challenged with MARV. 相似文献
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BRANT C. FAIRCLOTH ALLISON REID TERESA VALENTINE SOO HYUNG EO THERON M. TERHUNE TRAVIS C. GLENN WILLIAM E. PALMER CAMPBELL JOSEPH NAIRN JOHN P. CARROLL 《Molecular ecology resources》2005,5(2):387-389
We describe primers and polymerase chain reaction (PCR) conditions to amplify four dinucleotide, one trinucleotide, and three tetranucleotide microsatellite DNA loci from the bobcat (Lynx rufus). The primers were tested on 22 individuals collected from a population located within southwestern Georgia (USA). The primer pairs developed in this study yielded an average of 7.4 alleles per locus (range four to 10), an average observed heterozygosity of 0.60 (range 0.40 to 0.76), and an average polymorphic information content of 0.70 (range 0.51 to 0.78). 相似文献