This preview shows page 1. Sign up to view the full content.
Unformatted text preview: Structural biology of viruses
Biophysical Chemistry 1, Fall 2010 Coat proteins
Reading assignment: Chap. 15 Virus particles self-assemble from coat monomers
Virus Structure and Function 451 FIGURE 15.1
Schematic drawings of virus particles. Left: Poliovirus, a simple icosahedral virus
with a diameter of about 300 Å (based on a crystal structure). Right: Flavivirus, an enveloped
virus with a crystal diameter of about 470 Å (based on a cryo-EM model with models of coat
protein molecules from a crystal structure fitted into the cryo-EM density). The colors denote
subunits in different environments as discussed below. From VIPER (http://viperdb.scripps.edu/). membrane proteins themselves or with an inner symmetric protein layer. Nonenveloped viruses normally have either helical or icosahedral symmetry. Some Icosahedral coats are the most common ones
452 A Textbook of Structural Biology FIGURE 15.2
An icosahedron showing the positions of the five-, three- and two-fold symmetry
axes. The repeated unit is marked in gray. This is only one of many possible choices of the
repeated unit. The basis of the theory is that it is possible to form six-fold and five-fold interactions with similar contacts between subunits. A plane triangular net with
six-fold contacts can be transformed into an icosahedron if some of the six-fold
contacts are replaced by five-fold contacts in a regular manner. The five-fold
contacts create curvature, and depending on the position of these five-fold axes,
icosahedra with different numbers of triangles are formed. Caspar and Klug Interactions can be viewed in two dimensions
Virus Structure and Function 453 T=7
T=4 k 1, 2
1, 1 1, 0 FIGURE 15.3 2, 0 h Triangular nets where points of six-fold symmetry have been selected in a regular Various triangulation numbers
454 A Textbook of Structural Biology FIGURE 15.4
Viruses with triangulation numbers 1, 3, 4, 7 and 13 showing their relative sizes.
The surface of the virus particles is shaded according to its distance from the center, darker being
closer. Some particles have an icosahedral shape, but the particles all have icosahedral symmetry. The drawings are based on the crystal structures (from left to right) of satellite tobacco
necrosis virus, phage MS2, Nudaurelia capensis ω virus, phage HK97 and the bluetongue virus.
From VIPER (http://viperdb.scripps.edu/). metry. The drawings are based on the crystal structures (from left to right) of satellite tobacco necrosis virus, phage MS2, Nudaurelia capensis ω virus, coat monomers
Virus particles self-assemble from phage HK97 and the bluetongue virus.
From VIPER (http://viperdb.scripps.edu/). FIGURE 15.5
The jellyroll fold in a viral coat protein subunit (satellite tobacco necrosis virus,
PDB: 2BUK). viruses are mainly responsible for the shape and size of the virus particles and
are able to form five-fold, three-fold and two-fold contacts. When multiples of
60 chemically identical subunits form the shell, the molecules must be able to
form at least slightly different contacts in a correct way to make well-ordered
capsids with icosahedral symmetry. The first structures of virus particles to be Interdigitation often stabilizes coats 456 A Textbook of Structural Biology FIGURE 15.7
The arrangement of 18 subunits around the three-fold (quasi-six-fold) axis in the
southern cowpea mosaic virus. The partially ordered arm in one of the subunits (marked in red)
interacts with arms from symmetry-related subunits at the three-fold axis (beta annulus, indicated
with an arrow). In this virus, the N-terminal 23 amino acids are disordered in all subunits. This
region contains several positively charged residues and probably interacts with the viral RNA,
which is asymmetric. Cell entry: hemagglutinins A Textbook of Structural Biology Cell entry: simple viruses
Virus Structure and Function 459 FIGURE 15.9
The E1 protein from the Semliki Forest virus, an alphavirus (PDB: 1I9W). The coloring is from N-terminal (blue) to C-terminal (red). The fusion peptide is the loop at the extreme
right of the molecule and is hidden through contacts to another protein in a homodimer. The
anchor to the viral membrane is at the C-terminus of the protein, but this part of the protein was
removed before crystallization and is therefore not seen here. in the host cell that allows the particle or the viral genome to pass through the cellular or endosomal membrane.
Picornaviruses, including poliovirus and rhinovirus (the common cold
virus), are simple viruses with only a few structural and non-structural proteins. Their entry mechanisms have been studied as one of the possible
ways of finding drugs to prevent viral infections. The mature poliovirus parti- Cell entry: poliovirus architecture A Textbook of Structural Biology FIGURE 15.10
N-terminal arms in the poliovirus. Left: The repeating unit (protomer) as seen
from the inside of the shell. The N-terminal extensions are shown in dark shading, while the main
part of the subunit is pale. The N-termini of VP1 and VP3 are bound to the main parts of VP3
and VP1, respectively, while the remaining N-terminal of VP2, after cleavage of VP4, is bound
to the subunit itself. Right: Packing of subunits around the five-fold axis as seen from the FIGURE 15.11 The MS2 coat protein dimer as seen in a radial direction from the outside of the particle. A segment of RNA is shown (purple) (PDB: 2BU1).
Getting the rightbound RNAback into the virus FIGURE 15.12
The binding of the RNA hairpin by the MS2 dimer (PDB: 1ZDI). Adenine
bases −10 and −4 are bound in corresponding pockets in the two monomers of the dimer,
and uracil base −5 is stacked to a tyrosine sidechain in one of the subunits. To the right, the
secondary structure of the hairpin is shown. The initiation codon of the replicase subunit is
boxed. component ispackaging in bacteriophage using scaffolding proteins that
Genome added in turn. The head is assembled (a) (b)
Tail tube Tail sheath Long tail fibers Base plate with
short tail fibers FIGURE 15.13
Phage T4. To the left is an electron micrograph of the phage (courtesy of R.
Duda, Pittsburgh). The main parts of the virion are labeled in the schematic view to the right. Some details of the packing apparatus Virus Structure and Function 463 FIGURE 15.14
The trimeric gp5-gp27 complex. The three monomers of gp5 are in red, blue
and yellow, and the monomers of gp27 in green, brown and purple. The lysozyme domain of
gp5 is at the upper part of the triple beta helix that forms the stalk of the molecule. FIGURE “baseplate”
The T415.14 andTthe trimeric gp5-gp27 complex. The three monomersThegp5 are indomain of
monomers of gp27 in green, brown and purple.
gp5 is at the upper part of the triple beta helix that forms the stalk of the molecule. FIGURE 15.15
Fitting of several proteins from the T4 baseplate into a cryo-EM map. The gp5gp27 complex is at the center of this model. gp5 is in yellow and gp27 (barely visible) in
turquoise. The other proteins that are modeled are gp9 (blue), gp8 (red), gp11 (orange), and
gp12 (purple). (Courtesy of Thomas Goddard, University of San Francisco.) are degraded and leave before a portal protein injects the DNA. The tail is assembled separately and joined to the DNA-packed head.
In the mature virion, the tail is loaded like a spring. Interactions between the
short tail fibers and the bacterium lead to conformational changes in the baseplate. ...
View Full Document