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Building 3-D Virus Structures

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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
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