Three-dimensional structures virus

Colman, P.M., et al. Three-dimensional structure of a complex of antibody with influenza virus neuraminidase. Nature 326 358-363, 1987. 

A nucleic acid can never code for a single protein molecule that is big enough to enclose and protect it. Therefore, the protein shell of viruses is built up from many copies of one or a few polypeptide chains. The simplest viruses have just one type of capsid polypeptide chain, which forms either a rod-shaped or a roughly spherical shell around the nucleic acid. The simplest such viruses whose three-dimensional structures are known are plant and insect viruses the rod-shaped tobacco mosaic virus, the spherical satellite tobacco necrosis virus, tomato bushy stunt virus, southern bean mosaic vims. 

Since all members of this family of RNA phages have homologous coat proteins, their subunits are expected to have the same three-dimensional structure. It remains to be seen if the MS2 fold is also present in any other unrelated viruses. The fold is so far unique for the MS2 subunit, but similar structures have been observed in other proteins such as the major histocompatibility antigen, HLA, which was discussed in Chapter 15. 

Acharya, R., et al. The three-dimensional structure of foot-and-mouth disease virus at 2.9 A resolution. Nature 337 709-716, 1989. 

Crystal structures of the NS5B polymerase alone and in complexes with nucleotide substrates have been solved and applied to discovery programs (Ago et al. 1999 Bressanelli et al. 2002 Bressanelli et al. 1999 Lesburg et al. 1999 O Farrell et al. 2003). From these studies, HCV polymerase reveals a three-dimensional structure that resembles aright hand with characteristic fingers, palm, and thumb domain, similar to the architectures of the RNA polymerases of other viruses. However, none of these experimental structures contained the ternary initiation complex with nu-cleotide/primer/template, as obtained with HIV RT. Accordingly, HCV initiation models have been built using data from other viral systems in efforts to explain SAR (Kozlov et al. 2006 Yan et al. 2007). 

Varghese IN, Colman PM (1991) Three-dimensional structure of the neuraminidase of influenza virus A/Tokyo/3/67 at 2.2 A resolution. 1 Mol Biol 221 473 86 Varghese IN, Laver WG, Colman PM (1983) Structure of the influenza virus glycoprotein antigen neuraminidase at 2.9 A resolution. Nature 303 35 0 Varghese IN, McKimm-Breschkin IL, Caldwell IB, Kortt AA, Colman PM (1992) The structure of the complex between influenza virus neuraminidase and sialic acid, the viral receptor. Proteins 14 327-332... 

For example, with the crystal structure of the aspartyl protease from human immundeficiency virus (HIV-1) in 1989 came the opportunity to design molecules to block this important enzyme that acts as a molecular scissors. HIV is the virus responsible for AIDS. Essential to viral replication, the HIV protease cuts long strands composed of many proteins into the functional proteins found in mature virus particles. This proteolysis occurs at the very end of the HIV replication cycle (Figure 7-1). The three-dimensional structural information derived from the x-ray crystal structure, combined with computer modeling techniques, allowed chemists to design potent, selective inhibitors of the protease enzyme (Figure... 

Fig. 3. The hepatitis delta virus ribozyme. A Secondary structure of the genomic HDV ribo-zyme RNA used for the determination of the crystal structure [37]. The color code is reflected In the three dimensional structure B of this ribozyme. PI to P4 indicate the base-paired regions. Nucleotides in small letters indicate the U1 A binding site that was engineered into the ribozyme without affecting the overall tertiary structure. The yellow region indicates close contacts between the RNA and the U1 A protein...

The abnormal deposits found in the brains of CJD victims consist of an abnormal isoform of PrP. Prion protein is normally found in cells. Detailed structural studies show that normal cellular PrP (PrP ) is a soluble protein whose conformation is rich in a-helices with very little P-sheet. The PrP protein extracted from the brains of CJD victims (i.e., PrP ) is identical in primary amino acid sequence to the normal PrP (PrP ). However, PrP has a much greater content of P-sheet conformation with little a-helical structure. Thus PrP is neurotoxic because of its three-dimensional structure. When the prion protein is predominantly in an a-helical conformation it is nontoxic when the prion protein is predominantly in a P-sheet conformation, it kills neurons. The prion protein is thus made neurotoxic not by its amino acid composition but by its conformation. This concept is both fascinating and terrifying. Prion diseases are transmissible thus prions are infectious agents. However, prions are not like bacteria or viruses, or other infectious microbes—they are simply protein molecules. Prions are not microbes with cell membranes and nucleic acids they are not living things. Indeed, prions are not even infectious molecules, they are infectious molecular shapes. 

Herber, I.S. Sigal, P.L. Darke, and IP. Springer, Three-dimensional structure of aspartyl protease from human immunodeficiency virus HIV-1. Natnre, 1989.337(6208) 615-20. 

Nanostructures are, literally, facts of life in biology. Proteins, viruses, and bacteria are nanosized, three-dimensional structures which have been self assembled from smaller subunits. Although individual atoms in the subunits (polypeptides, for example) are covalently linked, assembly of the subunits is maintained by non-covalent (van der Waals, hydrogen-bonding, electrostatic, and hydrophobic) interactions. 

The materials capable of stimulating the lymphoid tissues to produce antibodies are termed antigens and comprise bacterial and viruses as well as some smaller molecular entities. However, the response is not to the intact organisms but rather to some specific parts which have characteristic three-dimensional structures, the epitopes, and this sensitivity to structure is a characteristic feature of the immune response. Once an animal is in contact with an epitope the response can be in the circulatory or humoral system or directly as a cell-mediated response, but it is exquisitely sensitive to the specific antigen and rarely to any other. 

One of the smallest of the encapsulated RNA-containing viruses is the satellite tobacco necrosis virus. It replicates only when the plant is also infected with the larger tobacco necrosis virus. The satellite virus, whose three-dimensional structure is known from X-ray diffraction studies,485 contains a 1200-nucleotide strand of RNA which encodes a 195-residue protein. 

Its role is to cut a hole in the bacterial cell wall to permit injection of the virus own DNA. Egg white lysozyme, the first enzyme for which a complete three-dimensional structure was determined by X-ray diffraction,55 is a 129-residue protein. 

Valegard, K., L. Liljas, K. Fridborg, and T. Unge, The three-dimensional structure of the bacterial virus MS2. Nature 345 36-41, 1990. 

Genomics has motivated a significantly increased effort in protein structure determination and structure prediction. The accumulation of three-dimensional protein structures has increased dramatically in the past few years. In 1999, approximately 2500 structures were added to the Protein Data Bank (PDB), a 20-fold increase over the 116 structures added to the PDB in 1989 (www.rcsb.org). Over 10,000 three-dimensional structures of proteins, peptides, and viruses now reside in the PDB. Of these, the number of prokaryotic proteins with structural information is significant in E. coli, 771 of the 4288 predicted proteins have significant similarity to a protein with known three-dimensional structure [60]. 

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