Virus Structure Tutorial Shuchismita Dutta, Ph.D. RCSB PDB, 2008 Introduction • Viruses can cause a variety of diseases from common cold and the flu to serious illnesses such as AIDS, dengue fever, measles, small pox and bird flu. • All viruses infect cells and hijack the host cellular machinery for their own benefit. • Learning about the biology and structure of viruses can help us better understand the diseases that they cause, their prevention and treatment. Goal • Introduction to viruses – what they are made of, how do they survive and propagate. • Virus structures – shape and symmetric interaction of proteins, nucleic acids. • Hands-on activities • List of related resources and additional reading material. • Take home message: The shape and structure of proteins are specific for their function. Overview • Information – Protein Data Bank – Viruses • Building virus models – Paper models – Marshmallow models • Dengue virus – Virus maturation • Possible directions for lesson plans Basic Information 1 2 3 What is a virus? • Organism that causes diseases – Common cold – Flu – AIDS – Bird flu – Polio HIV Smallopx virus Aeromonas virus 31 Herpes simplex virus Electron micrographs of viruses. Influenza virus Orf virus What do Viruses look like? Tailed phages Are viruses living or non-living? (A typical virus life-cycle) http://www.microbiologybytes.com/introduction/structure.html http://www.cliffsnotes.com/WileyCDA/CliffsReviewTopic/Viral-Structure-and-Replication.topicArticleId-8524,articleId-8448.html Viral Infection and Immunity Poliovirus and Rhinovirus August 2001 Molecule of the Month Building Icosahedral Viruses What is an Icosahedron? Icosahedron: a geometric solid with twenty faces. Each face is an equilateral triangle and every vertex of the icosahedron is formed by five triangular faces. Edges 30; Vertices 12; Faces 20 The Marshmallow model Students make marshmallow icosahedrons at Princeton Science & Engineering Expo The Paper Model Students make marshmallow icosahedrons at Princeton Science & Engineering Expo The Story of Dengue Virus Dengue Virus • • • • Single-stranded RNA virus Causes dengue hemorrhagic fever Transmitted by mosquitoes (Aedes aegypti) Serotypes (DEN-1, 2, 3, 4) Dengue Virus Nature Structural Biology 10, 907 - 912 (2003) Where? World distribution of dengue viruses and their mosquito vector, Aedes aegypti, (2005) Life Cycle of Dengue Virus Structural changes in envelope protein, icosahedral shell: •Fusion –antiparallel homodimers to parallel homotrimers •Maturation – conformational change of immature trimers to homodimers followed by protease cleavage (by furin) to form mature antiparpllel dimers Nature Reviews Microbiology 3, 13-22 (January 2005) Maturation of Dengue Virus Science 28 March 2008:Vol. 319. no. 5871, pp. 1834 - 1837 Maturation & Fusion Molecule of the Month, July, 2008 Nature Reviews Microbiology 3, 13-22 (January 2005) Possible Directions for Lesson Plans A Lesson on Icosahedral Viruses • • • • • Shapes of proteins (Introduction to PDB) What is a virus? Shapes of viruses Building 3-D models of icosahedral viruses Answering questions about viruses and the icosahedral virus models. • Research on a specific disease caused by a virus (e.g. Dengue Fever) Vaccines and Antivirals •Infection, Prevention & Treatment •Rhinovirus or Flu virus or HIV etc. Protein Structure Transcription/Translation •Structure of proteins in virus shells •Use of symmetry in assembling viruses •How viruses hijack host cells •Viruses and cancer Viruses Math & Geometry Genetics & Mutation •Icosahedrons, •helices etc. •Evolution in viruses •Why antiviral treatments need to evolve too Biotechnological uses of Viruses •Protein expressing, •gene therapy Acknowledgements Operated by two members of the RCSB: The RCSB PDB is a member of the Supported by: NIGMS