Michael G Rossmann

Purdue University, ウェストラファイエット, Indiana, United States

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Publications (473)3309.87 Total impact

  • Xinzheng Zhang, Lei Sun, Michael G Rossmann
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    ABSTRACT: Dengue virus is the causative agent of dengue virus fever. It infects about 400 million people per year and leads to about 21,000 deaths annually. There is available neither a fully successful vaccine nor a successful drug therapy. Some dengue virus serotypes undergo a temperature dependent conformational change from a 'smooth' form at lower temperatures to a 'bumpy' form at temperatures approaching 37°C, the human body temperature. The bumpy structure is less stable and is probably an intermediate in the formation of a fusogenic virus particle. Copyright © 2015 Elsevier B.V. All rights reserved.
    Current Opinion in Virology 06/2015; 12. DOI:10.1016/j.coviro.2015.04.006 · 6.30 Impact Factor
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    ABSTRACT: Mimivirus was initially identified as a bacterium because its dense, 125-nm-long fibers stained Gram-positively. These fibers probably play a role during the infection of some host cells. The normal hosts of Mimivirus are unknown, but in the laboratory Mimivirus is usually propagated in amoeba. The structure of R135, a major component of the fibrous outer layer of Mimivirus, has been determined to 2-Å resolution. The protein's structure is similar to that of members of the glucose-methanol-choline oxidoreductase family, which have an N-terminal FAD binding domain and a C-terminal substrate recognition domain. The closest homolog to R135 is an aryl-alcohol oxidase that participates in lignin biodegradation of plant cell walls. Thus R135 might participate in the degradation of their normal hosts, including some lignin-containing algae. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Structure 04/2015; DOI:10.1016/j.str.2015.03.023 · 6.79 Impact Factor
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    ABSTRACT: Giant viruses are protist-associated viruses belonging to the proposed order Megavirales; almost all have been isolated on Acanthamoeba sp. Their isolation in humans suggests that they are part of the human virome. Using a high-throughput strategy to isolate new giant viruses on their original protozoa hosts, we obtained eight isolates of a new giant viral lineage on Vermamoeba vermiformis, the most common free-living protist found in human environments. This new lineage was proposed to be a Faustovirus. The prototype member Faustovirus E12 forms icosahedral virions of ≈200 nm in size that are devoid of fibrils and that encapsidate a 466 kilobase pair-long genome encoding 451 predicted proteins. Of these, 164 are found in the virion. The phylogenetic analysis of core viral genes shows that Faustovirus is distantly related to the mammalian pathogen African swine fever virus, but encodes ≈3 times more mosaic gene complements. About two-thirds of these genes do not show significant similarity to any known proteins. These findings show that expanding the panel of protists to discover new giant viruses is a fruitful strategy. By using for the first time Vermamoeba, a protist living in humans and their environment, we isolated eight strains of a new giant virus we named Faustovirus. The genomes of these strains were sequenced, showing that the faustoviruses are related but different from the vertebrate pathogen African swine fever virus (ASFV), which belongs to the family Asfarviridae. Moreover, the Faustovirus gene repertoire is ≈3 times larger than that of ASFV and comprises ≈ two-thirds ORFans. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Journal of Virology 04/2015; 89(13). DOI:10.1128/JVI.00115-15 · 4.65 Impact Factor
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    ABSTRACT: Enterovirus D68 (EV-D68) is a member of Picornaviridae and is a causative agent of recent outbreaks of respiratory illness in children in the United States. We report here the crystal structures of EV-D68 and its complex with pleconaril, a capsid-binding compound that had been developed as an anti-rhinovirus drug. The hydrophobic drug-binding pocket in viral protein 1 contained density that is consistent with a fatty acid of about 10 carbon atoms. This density could be displaced by pleconaril. We also showed that pleconaril inhibits EV-D68 at a half-maximal effective concentration of 430 nanomolar and might, therefore, be a possible drug candidate to alleviate EV-D68 outbreaks. Copyright © 2015, American Association for the Advancement of Science.
    Science 01/2015; 347(6217):71-4. DOI:10.1126/science.1261962 · 31.48 Impact Factor
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    ABSTRACT: Flaviviruses undergo large conformational changes during their life cycle. Under acidic pH conditions the mature virus forms transient fusogenic trimers of E glycoproteins that engage the lipid membrane in host cells to initiate the viral fusion and nucleocapsid penetration into the cytoplasm. However, the dynamic nature of the fusogenic trimer has made the determination of its structure a challenge. Here we have used Fab fragments of the neutralizing antibody DV2-E104 to stop the conformational change of Dengue virus at an intermediate stage of the fusion process. Using cryo-electron microscopy, we show that in this intermediate stage the E glycoproteins form 60 trimers that are similar to the predicted "open" fusogenic trimer.
    Journal of Virology 10/2014; 89(1). DOI:10.1128/JVI.02411-14 · 4.65 Impact Factor
  • Moh Lan Yap, Michael G Rossmann
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    ABSTRACT: ABSTRACT Bacteriophage T4 is the most well-studied member of Myoviridae, the most complex family of tailed phages. T4 assembly is divided into three independent pathways: the head, the tail and the long tail fibers. The prolate head encapsidates a 172 kbp concatemeric dsDNA genome. The 925 Å-long tail is surrounded by the contractile sheath and ends with a hexagonal baseplate. Six long tail fibers are attached to the baseplate's periphery and are the host cell's recognition sensors. The sheath and the baseplate undergo large conformational changes during infection. X-ray crystallography and cryo-electron microscopy have provided structural information on protein-protein and protein-nucleic acid interactions that regulate conformational changes during assembly and infection of Escherichia coli cells.
    Future Microbiology 10/2014; 9(12):1319-27. DOI:10.2217/fmb.14.91 · 3.82 Impact Factor
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    ABSTRACT: Chloroviruses infect their hosts by specifically binding to and degrading the cell wall of their algal hosts at the site of attachment, using an intrinsic digesting enzyme(s). Chlorovirus PBCV-1 stored as a lysate survived longer than virus alone, suggesting virus attachment to cellular debris may be reversible. Ghost cells (algal cells extracted with methanol) were used as a model to study reversibility of PBCV-1 attachment because ghost cells are as susceptible to attachment and wall digestion as are live cells. Reversibility of attachment to ghost cells was examined by releasing attached virions with a cell wall degrading enzyme extract. The majority of the released virions retained infectivity even after re-incubating the released virions with ghost cells two times. Thus the chloroviruses appear to have a dynamic attachment strategy that may be beneficial in indigenous environments where cell wall debris can act as a refuge until appropriate host cells are available.
    Virology 09/2014; 466. DOI:10.1016/j.virol.2014.07.002 · 3.28 Impact Factor
  • Michael G Rossmann
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    ABSTRACT: I describe my gradually evolving role as a scientist from my birth in Frankfurt (Germany) to my education in the UK, my post-doc years and my experiences as an independent investigator at Purdue University1. I discuss the significance of my post-doctoral work in Minnesota where I had my first encounter with an electronic computer and subsequently in Cambridge where I participated in the first structure determination of proteins. After six years back in England my family moved to Indiana (USA) where my home remains to this day. At Purdue University I first studied the structure of enzymes and in the process I discovered the organization and slow evolution of protein domains, each with a specific function. With this success I started what had been on my mind already for a long time, namely the structural analysis of viruses. Initially we studied plant viruses but then switched to small RNA animal viruses, discovering that some plant and animal RNA viruses have closely similar structures and therefore presumably had a common evolutionary origin. Next I became interested in somewhat larger viruses that had lipid membrane envelopes. In turn that has led to the study of very large dsDNA viruses as big as small bacteria as well as studies of bacterial viruses that require complex molecular motors for different parts of their life cycle. While developing crystallographic techniques for the study of viruses it has become progressively more apparent that electron microscopy is an important new tool that is likely to eclipse x-ray crystallography in the next decade.
    Physica Scripta 09/2014; 89(9). DOI:10.1088/0031-8949/89/9/098005 · 1.30 Impact Factor
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    Yue Liu, Michael G Rossmann
    Protein & Cell 08/2014; 5(9). DOI:10.1007/s13238-014-0092-6 · 2.85 Impact Factor
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    ABSTRACT: The bacteriophage T4 baseplate is the control center of the virus, where the recognition of an E. coli host by the long tail fibers is translated into a signal to initiate infection. The short tail fibers unfold from the baseplate for firm attachment to the host, followed by shrinkage of the tail sheath that causes the tail tube to enter and cross the periplasmic space ending with injection of the genome into the host. During this process, the 6.5 MDa baseplate changes its structure from a "dome" shape to a "star" shape. An in vitro assembled hubless baseplate has been crystalized. It consists of six copies of the recombinantly expressed trimeric gene product (gp) 10, monomeric gp7, dimeric gp8, dimeric gp6 and monomeric gp53. The diffraction pattern extends, at most, to 4.0 Å resolution. The known partial structures of gp10, gp8, and gp6 and their relative position in the baseplate derived from earlier electron microscopy studies were used for molecular replacement. An electron density map has been calculated based on molecular replacement, single isomorphous replacement with anomalous dispersion data and 2-fold non-crystallographic symmetry averaging between two baseplate wedges in the crystallographic asymmetric unit. The current electron density map indicates that there are structural changes in the gp6, gp8, and gp10 oligomers compared to their structures when separately crystallized. Additional density is also visible corresponding to gp7, gp53 and the unknown parts of gp10 and gp6.
    Journal of Structural Biology 07/2014; 187(2). DOI:10.1016/j.jsb.2014.06.008 · 3.37 Impact Factor
  • Lei Sun, Michael G Rossmann, Bentley A Fane
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    ABSTRACT: Although the φX174 DNA pilot protein H is monomeric during procapsid assembly, it forms an oligomeric tube on the surface of host cells. Reminiscent of a double-stranded DNA phage tails in form and function, the H-tube transports the single-stranded φX174 genome across the E. coli cell wall. The 2.4 Å resolution, H-tube crystal structure suggests functional and energetic mechanisms, which may be common features of DNA transport through virally encoded conduits.
    Journal of Virology 07/2014; 88(18). DOI:10.1128/JVI.00291-14 · 4.65 Impact Factor
  • Thomas Klose, Michael G Rossmann
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    ABSTRACT: Abstract Nucleocytoplasmic large dsDNA viruses (NCLDVs) encompass an ever-increasing group of large eukaryotic viruses, infecting a wide variety of organisms. The set of core genes shared by all these viruses includes a major capsid protein with a double jelly-roll fold forming an icosahedral capsid, which surrounds a double layer membrane that contains the viral genome. Furthermore, some of these viruses, such as the members of the Mimiviridae and Phycodnaviridae have a unique vertex that is used during infection to transport DNA into the host.
    Biological Chemistry 07/2014; 395(7-8):711-719. DOI:10.1515/hsz-2014-0145 · 2.69 Impact Factor
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    ABSTRACT: Japanese encephalitis virus (JEV), a mosquito-borne flavivirus that causes fatal neurological disease in humans, is one of the most important emerging pathogens of public health significance. JEV represents the JE serogroup, which also includes West Nile, Murray Valley encephalitis, and St. Louis encephalitis viruses. Within this serogroup, JEV is a vaccine-preventable pathogen, but the molecular basis of its neurovirulence remains unknown. Here, we constructed an infectious cDNA of the most widely used live-attenuated JE vaccine, SA14-14-2, and rescued from the cDNA a molecularly cloned virus, SA14-14-2MCV, which displayed in vitro growth properties and in vivo attenuation phenotypes identical to those of its parent, SA14-14-2. To elucidate the molecular mechanism of neurovirulence, we selected three independent, highly neurovirulent variants (LD50, <1.5 PFU) from SA14-14-2MCV (LD50, >1.5×105 PFU) by serial intracerebral passage in mice. Complete genome sequence comparison revealed a total of eight point mutations, with a common single G1708→A substitution replacing a Gly with Glu at position 244 of the viral E glycoprotein. Using our infectious SA14-14-2 cDNA technology, we showed that this single Gly-to-Glu change at E-244 is sufficient to confer lethal neurovirulence in mice, including rapid development of viral spread and tissue inflammation in the central nervous system. Comprehensive site-directed mutagenesis of E-244, coupled with homology-based structure modeling, demonstrated a novel essential regulatory role in JEV neurovirulence for E-244, within the ij hairpin of the E dimerization domain. In both mouse and human neuronal cells, we further showed that the E-244 mutation altered JEV infectivity in vitro, in direct correlation with the level of neurovirulence in vivo, but had no significant impact on viral RNA replication. Our results provide a crucial step toward developing novel therapeutic and preventive strategies against JEV and possibly other encephalitic flaviviruses.
    PLoS Pathogens 07/2014; 10(7):e1004290. DOI:10.1371/journal.ppat.1004290 · 8.14 Impact Factor
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    ABSTRACT: Alphaviruses can be serious, sometimes lethal human pathogens that belong to the family Togaviridae. Structures of human Venezuelan equine encephalitis virus (VEEV), an alphavirus, in complex with two strongly neutralizing antibody Fab fragments (F5 and 3B4C-4) have been determined using a combination of cryo-electron microscopy (cryo-EM) and homology modeling. Here we characterize these monoclonal antibody Fab fragments known to abrogate VEEV infectivity by binding to the E2 (envelope) surface glycoprotein. Both these antibody Fab fragments cross-link the surface E2 glycoproteins and, therefore, probably inhibit infectivity by blocking the conformational changes that are required for making the virus fusogenic. The F5 Fab fragment cross-links E2 proteins within one trimeric spike, whereas the 3B4C-4 Fab fragment cross-links E2 proteins from neighboring spikes. Furthermore, F5 probably blocks the receptor-binding site, whereas 3B4C-4 sterically hinders the exposure of the fusion loop at the end of the E2 B-domain.
    Journal of Virology 06/2014; 88(17). DOI:10.1128/JVI.01286-14 · 4.65 Impact Factor
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    Michael G Rossmann
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    ABSTRACT: A brief history is given of how X-ray diffraction data from crystals have been recorded. Today there are new possibilities, spawned by the availability of free electron lasers that produce powerful femtosecond long X-ray pulses.
    03/2014; 1(Pt 2):84-6. DOI:10.1107/S2052252514000499
  • Andrei Fokine, Michael G Rossmann
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    ABSTRACT: The tailed double-stranded DNA bacteriophages, or Caudovirales, constitute ~96% of all the known phages. Although these phages come in a great variety of sizes and morphology, their virions are mainly constructed of similar molecular building blocks via similar assembly pathways. Here we review the structure of tailed double-stranded DNA bacteriophages at a molecular level, emphasizing the structural similarity and common evolutionary origin of proteins that constitute these virions.
    Bacteriophage 02/2014; 4(1):e28281. DOI:10.4161/bact.28281
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    ABSTRACT: Antibodies were prepared by immunizing mice with empty, immature particles of human enterovirus 71 (EV71), a picornavirus that causes severe neurological disease in young children. The capsid structure of these empty particles is different from that of the mature virus and is similar to "A" particles encountered when picornaviruses recognize a potential host cell before genome release. The monoclonal antibody E18, generated by this immunization, induced a conformational change when incubated at temperatures between 4 °C and 37 °C with mature virus, transforming infectious virions into A particles. The resultant loss of genome that was observed by cryo-EM and a fluorescent SYBR Green dye assay inactivated the virus, establishing the mechanism by which the virus is inactivated and demonstrating that the E18 antibody has potential as an anti-EV71 therapy. The antibody-mediated virus neutralization by the induction of genome release has not been previously demonstrated. Furthermore, the present results indicate that antibodies with genome-release activity could also be produced for other picornaviruses by immunization with immature particles.
    Proceedings of the National Academy of Sciences 01/2014; 111(6). DOI:10.1073/pnas.1320624111 · 9.81 Impact Factor
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    ABSTRACT: Prokaryotic viruses have evolved various mechanisms to transport their genomes across bacterial cell walls. Many bacteriophages use a tail to perform this function, whereas tail-less phages rely on host organelles. However, the tail-less, icosahedral, single-stranded DNA ΦX174-like coliphages do not fall into these well-defined infection processes. For these phages, DNA delivery requires a DNA pilot protein. Here we show that the ΦX174 pilot protein H oligomerizes to form a tube whose function is most probably to deliver the DNA genome across the host's periplasmic space to the cytoplasm. The 2.4 Å resolution crystal structure of the in vitro assembled H protein's central domain consists of a 170 Å-long α-helical barrel. The tube is constructed of ten α-helices with their amino termini arrayed in a right-handed super-helical coiled-coil and their carboxy termini arrayed in a left-handed super-helical coiled-coil. Genetic and biochemical studies demonstrate that the tube is essential for infectivity but does not affect in vivo virus assembly. Cryo-electron tomograms show that tubes span the periplasmic space and are present while the genome is being delivered into the host cell's cytoplasm. Both ends of the H protein contain transmembrane domains, which anchor the assembled tubes into the inner and outer cell membranes. The central channel of the H-protein tube is lined with amide and guanidinium side chains. This may be a general property of viral DNA conduits and is likely to be critical for efficient genome translocation into the host.
    Nature 12/2013; DOI:10.1038/nature12816 · 42.35 Impact Factor
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    ABSTRACT: Rubella virus (RV) is a leading cause of birth defects due to infectious agents. When contracted during pregnancy, RV infection leads to severe damage in fetuses. Despite its medical importance, compared with the related alphaviruses, very little is known about the structure of RV. The RV capsid protein is an essential structural component of virions as well as a key factor in virus-host interactions. Here we describe three crystal structures of the structural domain of the RV capsid protein. The polypeptide fold of the RV capsid protomer has not been observed previously. Combining the atomic structure of the RV capsid protein with the cryoelectron tomograms of RV particles established a low-resolution structure of the virion. Mutational studies based on this structure confirmed the role of amino acid residues in the capsid that function in the assembly of infectious virions.
    Proceedings of the National Academy of Sciences 11/2013; DOI:10.1073/pnas.1316681110 · 9.81 Impact Factor
  • Pavel Plevka, Anthony J Battisti, Ju Sheng, Michael G Rossmann
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    ABSTRACT: Flaviviruses, such as dengue, West Nile, and yellow fever viruses, assemble as fusion-incompetent particles and subsequently undergo a large reorganization of their glycoprotein envelope resulting in formation of mature infectious virions. Here we used a combination of three-dimensional cryo-electron tomography and two-dimensional image analysis to study pleiomorphic maturation intermediates of dengue virus 2. Icosahedral symmetries of immature and mature regions within one particle were mismatched relative to each other. Furthermore, the orientation of the two regions relative to each other differed among particles. Therefore, there cannot be a specific pathway determining the maturation of all particles. Instead, the region with mature structure expands when glycoproteins on its boundary acquire suitable orientation and conformation to allow them to become a stable part of the mature region. This type of maturation is possible because the envelope glycoproteins are anchored to the phospholipid bilayer that is a part of flavivirus virions and are thus restricted to movement on the two-dimensional surface of the particle. Therefore, compounds that limit movement of the glycoproteins within the virus membrane might be used as inhibitors of flavivirus maturation.
    Journal of Structural Biology 11/2013; 185(1). DOI:10.1016/j.jsb.2013.11.001 · 3.37 Impact Factor

Publication Stats

26k Citations
3,309.87 Total Impact Points

Institutions

  • 1969–2015
    • Purdue University
      • Department of Biological Sciences
      ウェストラファイエット, Indiana, United States
  • 2011
    • Chiang Mai University
      • Department of Microbiology
      Amphoe Muang Chiang Mai, Chiang Mai, Thailand
    • Columbia University
      New York City, New York, United States
    • Penn State Hershey Medical Center and Penn State College of Medicine
      • Microbiology and Immunology
      Hershey, Pennsylvania, United States
  • 2004–2011
    • The Catholic University of America
      • Department of Biology
      Washington, Washington, D.C., United States
  • 2010
    • National Institute of Arthritis and Musculoskeletal and Skin Diseases
      Maryland, United States
    • Southern Research Institute
      Birmingham, Alabama, United States
  • 2009
    • French National Centre for Scientific Research
      • Laboratoire Information Génomique et Structurale (IGS)
      Lutetia Parisorum, Île-de-France, France
  • 1994–2009
    • Cornell University
      • College of Veterinary Medicine
      Ithaca, New York, United States
  • 2008
    • Case Western Reserve University
      • Institute of Pathology
      Cleveland, Ohio, United States
    • Universität Regensburg
      • Department of Medical Microbiology and Hygiene
      Ratisbon, Bavaria, Germany
  • 2007
    • Universidad Autónoma de Madrid
      Madrid, Madrid, Spain
  • 2000
    • The University of Manchester
      Manchester, England, United Kingdom
  • 1996
    • National Institutes of Health
      베서스다, Maryland, United States
  • 1993
    • Justus-Liebig-Universität Gießen
      • Institut für Virologie
      Gießen, Hesse, Germany
  • 1991
    • The University of Warwick
      • Biological Sciences
      Coventry, England, United Kingdom
  • 1988
    • University of Wisconsin–Madison
      Madison, Wisconsin, United States
  • 1983
    • Uppsala University
      • Department of Cell and Molecular Biology
      Uppsala, Uppsala, Sweden
  • 1982
    • Mrc Harwell
      Oxford, England, United Kingdom
  • 1981
    • Universität Stuttgart
      Stuttgart, Baden-Württemberg, Germany