Viral Structure and Symmetry PDF

Helical symmetry -virus particles are formed by a single type of protein subunit arranged in a helical (spiral) structure. 10 nm: This represents the axial rise (or pitch) of the helix for one complet...

Helical symmetry -virus particles are formed by a single type of protein subunit arranged in a helical (spiral) structure. 10 nm: This represents the axial rise (or pitch) of the helix for one complete turn of the helical structure. It refers to the vertical distance the helix moves upward after a full rotation. Helix Subunit -Number of Units per Turn (u= 3): indicates that three protein subunits are required to make one complete turn of the helical structure. P=nxp i.e., Tobacco Mosaic Virus (TMV): Given: Axial rise per subunit for TMV is typically around p =0.14 nm Number of subunits per turn, n= 16.3 Calculation: P= 16.3 x 0.14 =2.28 Vesicular stomatitis viris (VSV) (see ppt) Figure 1(Left) -Cross-Section of the Nucleocapsid This shows a cross-sectional view of the viral nucleocapsid. The N protein (nucleoprotein) is wrapped around the viral RNA (shownas agreenstrand). The RNA is tightly bound by multiple copies of the N protein, forning a helical structure. This type of arrangement is typical for negative-strand RNA viruses like VSV. o The scale bar of 100 À (angstroms) represents the diameter of the nucleocapsid, indicating the compactness of the structure. Figure 2 (Middle)-DetailedStructure ofN Protein Bound to RNA o Detailed atomic-level view of the interaction between the N protein and the viral RNA. Each N protein is responsible for binding 9 nucleotides of RNA, ensuring that the RNA is encapsulated efficiently within the viral particle. o The protein is color-coded, with different domains of the N protein shown in red, yellow, and orange. Figure 3 (Right) -3D Reconstructionof the Vesicular Stomatitis Virus o 3D reconstruction of the complete VSV particle, which highlights the helical nucleocapsid structure. The outermost layers of the virus, represented in colors, indicate the complex arrangementof the N-RNAcomplex. The reconstruction demonstrates three distinct regions of the virus: the Tip, Trunk,and Base of the virus particle. Enveloped RNA Viruseswith (-) ssRNA and Helical Capsids Paramyxoviridae (Measles and Mumps viruses): o Thenucleocapsid (yellow and green in the diagram)is surrounded by an outer lipid envelopethat is studded with glycoproteins. Rhabdoviridae (Rabiesvirus): o Thevirus is bullet-shaped, with the nucleocapsid tightly coiled inside. Orthomyxoviridae (Influenza virus): o Influenza viruses contain segmented RNA genomes that are wrapped by nucleoproteins, forming multiple helical nucleocapsids. o The segmented genome shown to be surrounded by the viral matrix is protein (purple), and the RNA polymerase complex (PB2,PB1, PA) helps initiate transcription. Filoviridae (Ebola viruses): o Ebola vírus has a characteristic long, thread-like (filamentous) structure, with the RNA genome tightly packed into a helical nucleocapsid. Nucleocapsid: encapsulates the viral RNA, The nucloocapsid is the core structure that Composed of nucleoprotein (NP)bound to the RNA. Lipid Envelope: a lipid bilayer thatis acquired from the host Surrounding the nucleocapsid, there is membrane during viral replication. This lipid envelope isembedded with viral cell which are crucial for attachment to andentry into host cells. glycoprotoins, Nucleoprotein(N): forming a helical nucleocapsid,which gives the RNA its Binds the viral RNA, complex is enclosed within a lipid spiralstructure. The helical RNA-nucleoprotein bilayer envelope. Spike proteins (S): protrude from the surface, giving the virus its crown-like appearance. Clue 1: have a specific and precise number of proteins, commonly in Round capsids multiples of 60. Capsidscan contain 60,180, 240, or 960 proteins. formation of symmetrical spherical structures This regular arrangementallows the even though the proteins themselves may have irregular shapes. Clue 2: forming the outer Viruses come in sizes, the capsid proteins (proteins different fall within the size range of 20-60 kilodaltons (kDa). shell) typically integrity, packing these proteins in a highly Viruses maintain consistent structural organized manner. that spherical capsids Watson and Crick's Conclusion:Watson and Crick hypothesized are built using icosahedral symmetry. 20triangular faces,and this allows viruses to An icosahedron is a polyhedron with unit of irregularly form a stable, symmetric, and round structure from a repeating shaped proteins. This minimizes the amount of genetic material needed to encode the capsid proteins while maximizing structural stability. This idea is central to how many viruses, such as poliovirus, create efficient, of protein size and shape. protective outer shells despite the limitations lcosahedral Structure: An icosahedron has 20 triangular faces, 12 vertices, and 30 edges. Each of the 20 faces is an equilateral triangle, which means all its sides are equal. This shape is one of the Platonic solids, known for its high degree of symmetry. Symmetry: The icosahed ron has multiple axes of symmetry: 5-fold symmetry axes: run through the vertices of the icosahedron, where five triangular facesmeet the points of a star). (like 3-fold symmetry axes:go through the centers of each triangular face, where three faces meet. 2-fold symmetry axes:pass through the midpoints of the edges, where two faces meet. Efficient Subunit Arrangement: One of the main reasons viruses adopt an icosahedral structure is that itallows them to form a closed shellwith the smallest number of ldentlcal proteln subunits.  Tne minimum number of subunits reguired to forma complete icosahedron is 60. This is because: Eachtriangular face of the icosahedron is made up of 3 subunits. With 20 faces, you need 20x3=60. structure allows the Using identical subunitsrepeated in this highly symmetrical enclose its genetic material without needing a large number of Virus to efficiently differentproteins. Why This Is Importantfor Viruses: Viruses often have limited genetic material, so they can't code for many different an icosahedral capsid, they can achieve a strong, Structural By forming proteins. stable structure with only one or a few types of proteins, repeated many times. both efficient and compact, using This symmetry ensures that the viral capsid is the genome while maintaining the structural the minimum resources to protect viral integrity required to survive in various environments. Head-to-Head and Tail-to-Tail Interactions: Head-to-Head:The "top" part of one subunit interacts with the "top" part of the neighboring subunit. the "bottom" parts of two neighboring subunits interact. Tail-to-Tail: structure, where the These identical interactions help form a closed, stable subunits fit together like pieces of a puzzle. T=1 (Triangulation Number = 1): The triangulation number (T) refers to the complexity howmany subunits form one triangular face in of the capsid's arrangement in terms of the icosahedral-like arrangement. meansthat each triangular face of the structure is made up of exactly 3 T=1 in viral capsids. Since protein subunits.This is the simplest possible arrangement T=1, 20 triangular faces of the the virus is composed of 60 subunits, with the icosahedron each consist of just 3 subunits. simple, as subunits are identical and InT=1 capsids, the capsid remains fairly all fit together uniformly. Example: Adeno-associated virus 2 has a capsid made of 60 identical protein subunits that The virus is small (25 nm) and contains a ssDNA form a T=1 icosahedral structure. genome. The capsid protects the genetic material and helps the virus infect host cells, with each capsid face formed by 3 identical proteins to create a symmetrical and stable structure. Quasiequivalence: When there are more than 60 capsid subunits, each of these subunits cannot all have identical surroundings in the same structural environment. However, they are placed in positions that are quasiequivalent. Quasiequivalence refers phenomenon where subunits occupy similar, but to the not identical, positions They form similar types of noncovalent in the capsid. interactions with their neighbors, but the exact nature of these interactions can vary slightly due to the larger and more complex structure. For viruses with more than 60 subunits, like those with T=3 symmetry, the structural unit often includes three identical proteins that are organized in a way that they occupyquasiequivalent positions. o T=3 Symmetry is a geometric organization seen in many icosahedral viruses. T=3 capsid, each triangular face of the icosahedronis subdivided into 3 smaller triangles consists of 180 subunits. Example: The Poliovirus is 30 nm in diameter. Its capsid consists of 60 protomers. Each protomeris composed of three proteins: VP1, VP2,and VP3. These 60 protomers together form 180 subunits that create the virus's icosahedral shell  Ine icosahedral structure of the virus is depicted. showing the T= 3 triangulation number, meaning there are three smaller triangles within each face of the icosahedron. Tne diagram indicates the fivefold (5x) and sixfold (6x)axes of symmetry, which are common in icOsahedral viruses. These symmetryaxes show how the structural units are repeated an organized manner across the capsid. in inthe lower-left corner, a zoomed-inview shows the arrangement of the proteins VP1 (red), VP2 (yellow),and VP3 (blue).These proteins form a structural unit or protomer that is repeated 60 times. Figure A: Cross-section of the Poliovirus Capsid (Space-Filling Representation) This is a cross-sectional view of the poliovirus capsid. The different layers of proteins are highlighted: 1. VP1 (blue) 2. VP2 (green) 3. VP3(red) 4. VP4 (yellow) These are found in space-filling model, representing how the proteins proteins form a dense shell around the RNA genome of the virus. You can see the large central cavity,where the viral RNA resides. VP4 decorates the inner surface of the capsid, suggesting that this protein has an internal role in stabilizing the capsid. Figure B:Surface Representation of the Poliovirus Capsid VP1 (blue) is located primarily at the fivefold axes of the icOsahedral structure. VP2 (green) and VP3 (red) alternate between fivefold and threefold axes, capsid. contributing to the triangular symmetry seen in the icosahedral o Canyons: Depressions encircling the plateaus. Plateaus: Elevated regions around the fivefold axes. These regions are critical for receptor binding during the virus's infection process. The interaction between these proteins is responsible for forming the characteristic icosahedral shape and stabilizing the viral particle. Figure C: Internal Interactions Among Capsid Proteins Myristate, a fatty acid (yellow), is attached to VP4, aiding in the interaction with VP1 andVP3. This lipid modification helps stabilize the capsid by anchoring VP4 to the inner surface of the capsid. The N-termini of five VP3 molecules are shown arranged in a tube-like manner around the fivefold axes. VP4 molecules interact with the B-sheets of VP1 and VP3, contributing to the stability of the capsid. These internal interactions between the capsid proteins, especially around the fivefold axes, are essential for stabilizing the structure. These contacts are finalized after proteolytic processing (breaking down of VPOinto VP2 and VP4), ensuring that the virus is stable during assembly and infection. SV40 (Simian Virus 40) The capsid of SV40 is made up of 360 individual VP1 proteins, which are grouped into 72 pentamers. These pentamers (clusters of 5VP1 proteins) are the building blocks of the capsid. InSV40, some pentamers are in contact with 5 neighboring pentamers, while others are in contact with 6neighbors. This uneven arrangement allows the capsid to form a stable spherical structure, while also enabling it to close up tightly around the viral DNA inside. Comparison with Other Viruses Many viruses use different strategies to package their DNA or RNA. For example, most viruses don't use histones, which is what makes SV40's minichromosome structure unique. By using histones, SV40 is better able to regulate its genome's structure and renlicatinn mimickinn how eukanntic celle treat their own DNA  Adenovirus Structure The capsid of adenovirus follows T=25 icosahedral symmetry. This notation elers to how the capsid is assembled, indicating a higher level of complexity and alarger number of protein subunits. Specifically, the adenovirus capsid contains 20 copies of the viral protein ll (hexon), which is the primary structural protein. Fibers at 12 vertices: Adenovirus has 12vertex points. wherefiber proteins protrude from the surface of the capsid. These fibers help the virus attach to host cells during infection. The fiber is composed of three domains: Knob: The tip of the fiber that interacts with host cell receptors. 1. 2. Shaft: The long, central part of the fiber. 3. Penton base: The base of the fiber where it attaches to the capsid. The adenovirus capsid is made up of various proteins, each with a specificfunction: 1. Hexon (Protein These are the primary structural proteins that form Il): the bulk of the capsid. They group into hexon trimers (clusters of three) that create the capsid's outer surface. 2. Penton: Located at the vertices of the capsid where the fibers attach. Pentons have twO Componehts: a. Penton base: The base at the vertex of the capsid where the fiber attaches. b. Fiber: The long protein that protrudes from the penton base and is involved in binding tothe host cell receptors. 3. Protein IX: Described as the "cement" proteinbecause it helps stabilize the capsid.The connection betweenpentons and hexons is relatively weak, so 4. Protein |Xacts like a glue, reinforcing these interactions to make the capsid more robust. 5. Protein Illa, VI, VII, VII: These proteins are internal to the capsid and help with various tasks, including stabilizing the core structure and assisting in packaging viral DNA. ReovirusArchitecture and Protein Layers The outer capsid is made up of protein subunits, which are critical for cell attachment and entry. These subunits include: o u1c + o3: These proteins form a major part of the outer layer. The u1c protein likely aids in destabilizing the host cellmembrane during viral entry. while g3 has roles in stabilizing the outer shell and may interact with immune system components. o1 + o2: These proteins also contribute to the outer shell, with o1 functioning as a fiber protein that extends from the surface and likely plays a role inbinding to cell surface receptors during infection. The inner capsid (often referred to as the core or subviral particle) is composed of a different set of proteins: o A1 + o2:These proteins form the structural basis of the core shell, with A1 being a major scaffolding protein. o A2: This protein is likely involved RNA synthesis and encapsulation of the in dsRNA genome within the core. often associated with RNA polymerase It is activity, allowing the virus to transcribe its genome once inside the host cell. The two different T numbers (T=13 and T=2) represent the structural complexity of the virus: T=13 Symmetry: The outer shell(composed of VP7 trimers, as shown in the right image) has T=13 symmetry, which is a more complex form of icosahedral symmetry.The number 13 refers to how many different ways the triangular faces can be arranged to form the fullcapsid. This outer layer contains VP7 trimers, which means three VP7 proteins come together at each icosahedral vertex. This arrangement provides strength and stability to the outer shell, protecting the virus from environmental stresses.  T=2 Symmetry: Theinnershell (composed of VP3 monomers) is simpler, with T=2 Symmetry. This inner core is critical for housing and organizing the and assOciated enzymes needed viral genonme for transcription once inside the host cel. General Structureof Tailed Head: The head is an Bacteriophages(Left Image) icoOsahedral capsid is consists 4 external proteins that form the capsid of: 2 core proteins within the capsid. structure. DNA andother internal proteins are packed inside the head, which is protected by the capsid. onnector: Below the head is a connector that atta ches the head to the tail. It is Composed of 4 proteins and serves as a bridge between the capsid and the tail. Gontractile Tail: The tail is a long, tube-like structure that aids in delivering the viral genome into the bacterial host. It is composed of: 1 protein in the outer sheath that contracts during infection. 1 protein inthe internal tube that directly delivers the viral DNA. Whiskers:These are structural proteins (1 protein) that help stabilize the bacteriophage during the attachment to the baterial surface. TailFibers and Baseplate: These structures, seen at the bottom, help the bacteriophage attach toabacterial surface and trigger DNAinjection. Tail Sheath:The outer yellow-green layer represents the contractile tail sheath Internal Tube: The internal red structure represents the hollow tube through which viral DNA once the tail sheath contracts. This part emphasizes the mechanicalfunction travels of the tail sheath,which undergoesa dramatic contraction, shortening and exposing the internal tube for DNA delivery. Detailed Surface Structure of the Tail Tube Molecular surface model of the tail tube, represented in different colors (green, blue, and red). The different colors correspond or regions of the tube, to diferent protein chains demonstrating how multiple protein chains work together to form the tail tube structure. This view highlights how the internal tube, made of tightly packed proteins, is constructed Secondary Structureof the Tail Tube Proteins The proteins are represented by ribbon structures showing the alpha-helices(spiral-like structures) and beta-sheets (flat, arrow-like structures) that are the building blocks of proteins. Iron lon: The smallorange sphere represents an iron ion bound by three protein chains. Iron ions often stabilize protein structures or are involved in catalytic prOcesses,although their exact role in this context might relate to maintaining the structural integrity of the tail tube. Herpes Simplex Virus (HSV)Capsid and Portal Complex: Structure and Role of Viral Proteins The HSV capsid is a highly organized structure made up of multiple viral proteins (VPs), with a diameter of approximately 200 nm and a T=16 icosahedral symmetry. The capsid has 12 fivefold (5-fold) vertices, one of which is unique as it forms a specialized portal through which the viral DNAenters and exits, Key Viral Proteins (VPs)and Their Roles in the Capsid: 1. - VP5 (Yellow) Major Capsid Protein VP5 is the main structural component of the capsid, responsible for forming its bulk. a. Functions: i. Hexons: VP5 forms the hexagonal capsomers (hexons) that make up most of the faces of the capsid.  II. Pentons: At the 12 fivefold vertices of the capsid, forms pentons, which VP5 are responsible for 2. points of structural creating these VP26 (Orange convergence. inthe atop the VP5 Diagram) - Capsid Stabilizing Protein - hexXons and helps to VP26 sits stabilize the entire a. capsid Functions: structure.. VP26 strengthens the interactions between VP5 units, maintaining the shape and robustness of the capsid. ii. VP26 is thought to help connect the capsid with the tegument layer, which is involved in viral assembly and stabilization. VP23 and VP19C (Bluein 3. proteins form triplexes, the Diagram) - Triplex Proteins -These two which are critical for maintaining capsid stability. a. Functions: Triplexes: VP23 and VP19C work together i. to form Complexes that sit between hexons and pentons. These triplexes act like "cement" that links the capsomers together, especiallyat regions of high stress, such as the fivefold vertices. The Portal Complex and Its Role in DNA Entry/Exit: In the HSV capsid, one of the 12 fivefold vertices is modified to function as a portal for viral DNA. This is a unique structural feature, as allows the it virus to control the flow of its genetic material during the viral lifecycle. This portal complex is made up of several specialized proteins, including UL17, UL25, and UL36C (green in the diagram), which help form a hole or channel through which the DNA can pass. Specific Proteins in the Portal: UL17 and UL25: These proteins help stabilize the capsid after the been packed, preventing premature release of viral DNA has the genome. UL36C: This protein is involved in the mechanics of DNA entry and exit, ensuring the DNA is correctly inserted into the capsid and later ejected into the host cell. 1. Envelope as a Lipid Bilayer from Host Cell: The viral envelope is derived from the host cell membrane, specifically during the budding process where the virus exits the host cell. Inthe image, the viral nucleocapsid (the structure that contains the viral genome) interacts with the host membrane (step 2). The envelope is a lipid bilayer that the virus acquires as it buds off from the host cell, seen in step 3. This lipid layer contains host-derived lipids but is virus-specific in its protein composition. 2. Envelope Acquired by Budding of Nucleocapsid: The viral genome does not encode instead, the virus "borrows" the machinery for synthesizing lipids; host cell's membrane as it leaves This envelope is obtained by the the cell. process of budding,where the viral nucleocapsid pushes against and eventually buds through membrane. a host Instep 1,the nucleocapsid approaches the cell membrane. In step begins to bud 2, it through the membrane, acquiring its envelope. The enveloped final shown in step 4, fully covered in virion is the lipid bilayer that originated from the membrane. host 3. Envelope Can Be from Any Cellular Membrane, but It Is Viruses can acquire Virus-Specific: envelopes from different types of cellular (e.g., plasma membrane, membranes endoplasmic reticulum, Golgi), but the proteins embedded specific in the envelope are unique to the virus. Viral glycoproteins are inserted into the host membrane before the virus out. buds The budding process (steps 2 and 3) shows how the nucle0capsid through the membrane to gain its buds envelope. The final virion (step 4)  4. Nucleocapsid Can Have Helical or The lcosahedralSymmetry: nucleocapsid, which contains the viral genome, can have shapeseither helical (spiral-like) different or icosahedral The nucleocapsid (20-sided). insidethe virus material that is (shownin green) represents the genomic packaged within the capsid (the inner protein shell). Snape of the nucleocapsid The will depend on the virus; for example,influenza uses ypically have helical symmetry,while herpesviruses often have icosahedral symmetry. Integral Membrane Glycoproteins Tnese are are embedded in the lipid membrane of the virus. Since proteins that many have a lipid envelope derived from the host cell membrane, viruses the viral glycoproteins span this membrane. Integral glycoproteins servevarious purposessuch as: Enabling the virus to recognizeand bind to receptors on host cells. 2. Facilitating the entry of the viral genome into the host cell. Ectodomain The ectodomain is the part of the glycoprotein that sticks out of the viral envelope, making it accessible to the external environment. This domain plays key roles in several critical viral functions: 1. Attachment: The ectodomainis responsible for recognizing andbinding to specific receptors on the surface of the host cell. This is the first step in viral entry. Example: The spike protein of coronaviruses binds to the ACE2 receptor on human cells. 2. Antigenic Sites: The immune system often targets the ectodomain because it is exposed. Antigenic sites are regions on the protein where antibodies can bind and neutralize the virus. However, viruses may mutate these. sites to escape immune recognition. 3. Fusion:After attachment, many viruses use the ectodomain to fuse their lipid envelope with the host cell membrane. This fusion allows the viral genetic material to enter the host cell. Example: The hemagglutinin protein in influenza viruses has a fusion peptide that promotes membrane fusion under specific conditions (like low pH in endosomes). Internal Domain The internal domain of the glycoprotein is located inside the viral envelope. This part of the glycoprotein is involved in: 1. Assembly: During the formation of new viral particles, the internal domain interacts with other viral proteins and components to help assemble the virus. It ensures that viral proteins, nucleic acids (RNA or DNA), and lipids are properly arrangedto form a functional virion (virus particle). 2. Signaling: Some viral glycoproteins may also transmit signals the to viral core, cOordinating steps in the virus's lifecycle, the host. like uncoating of the genome once inside Oligomeric Spikes Many viral glycoproteins form oligomeric complexes, meaning they come together in groups (often 2, 3, or more units) to function. Spikes: These glycoproteins project from the viral surfaceas spikesor protrusions. These spikes are essential for viral infectivity because they concentrate functional glycoproteins in specific regions, increasing the efficiency of attachment and fusion. They create a larger surface area for interaction with host cell receptors. Oligomerization: This increases the stability of the viral glycoprotein and makes the fusion process more effective. For instance, the spikes of influenza or coronaviruses form trimers (three glycoprotein molecules)to mediate and membrane fusion. attachment