Virus Structure Tutorial Shuchismita Dutta, Ph.D. RCSB PDB, 2008.
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Transcript of Virus Structure Tutorial Shuchismita Dutta, Ph.D. RCSB PDB, 2008.
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
Electron micrographs of viruses.
HIV Aeromonas virus 31 Influenza virus
Orf virusHerpes simplex virusSmallopx 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 RhinovirusAugust 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
Nature Reviews Microbiology 3, 13-22 (January 2005)
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
Maturation of Dengue Virus
Science 28 March 2008:Vol. 319. no. 5871, pp. 1834 - 1837
Nature Reviews Microbiology 3, 13-22 (January 2005)
Molecule of the Month, July, 2008
Maturation &
Fusion
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)
VirusesViruses
Protein Structure•Structure of proteins in virus shells•Use of symmetry in assembling viruses
Math & Geometry•Icosahedrons, •helices etc.
Vaccines and Antivirals•Infection, Prevention & Treatment•Rhinovirus or Flu virus or HIV etc.
Genetics & Mutation•Evolution in viruses•Why antiviral treatments need to evolve too
Biotechnological uses of Viruses•Protein expressing,
•gene therapy
Transcription/Translation•How viruses hijack host cells•Viruses and cancer
Acknowledgements
Operated by two members of the RCSB:
Supported by:
NIGMS
The RCSB PDB is a member of the