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
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HIV Influenza virus Aeromonas virus 31 Smallopx virus Herpes simplex virus Orf virus Electron micrographs of viruses. What is a virus? • Organism that causes diseases • Common cold • Flu • AIDS • Bird flu • Polio
Tailed phages What do Viruses look like?
http://www.microbiologybytes.com/introduction/structure.html Are viruses living or non-living? (A typical virus life-cycle) 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
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
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 Biology10, 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)
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 • Structure of proteins • in virus shells • Use of symmetry in • assembling viruses • Transcription/Translation • How viruses hijack host cells • Viruses and cancer Viruses • Math & Geometry • Icosahedrons, • helices etc. • Genetics & Mutation • Evolution in viruses • Why antiviral treatments need to evolve too • Biotechnological uses of Viruses • Protein expressing, • gene therapy
NIGMS Acknowledgements Operated by two members of the RCSB: The RCSB PDB is a member of the Supported by: