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J M Hogle

Publications and source records attributed to J M Hogle.

64 records · Page 4Linked to original sources
PubMed1988

Three-dimensional structure of poliovirus serotype 1 neutralizing determinants.

Antigenic mutants of poliovirus (Sabin strain, serotype 1) were isolated by the resistance of the virus to anti-Sabin neutralizing monoclonal antibodies. The amino acid replacements within the capsid protein sequence causing the altered antigenicity were identified for each of 63 isolates. The mutations cluster into distinct nonoverlapping peptide segments that group into three general immunological phenotypes on the basis of cross-neutralization analyses with 15 neutralizing anti-Sabin monoclonal antibodies. Location of the mutated amino acid residues within the three-dimensional structure of the virion indicates that the majority of these amino acid residues are highly exposed and located within prominent structural features of the viral surface. Those mutated amino acid residues that are less accessible to antibody interaction are often involved in hydrogen bonds or salt bridges that would stabilize the local tertiary structure of the antigenic site. The interactions of the peptide segments that form these neutralizing sites suggest specific models for the generation of neutralization-resistant variants and for the interaction between the viral surface and antibody.

Antibodies, Monoclonal↗
PubMed1986

Structure and assembly of turnip crinkle virus. I. X-ray crystallographic structure analysis at 3.2 A resolution.

The structure of turnip crinkle virus has been determined at 3.2 A resolution, using the electron density of tomato bushy stunt virus as a starting point for phase refinement by non-crystallographic symmetry. The structures are very closely related, especially in the subunit arm and S domain, where only small insertions and deletions and small co-ordinate shifts relate one chain to another. The P domains, although quite similar in fold, are oriented somewhat differently with respect to the S domains. Understanding of the structure of turnip crinkle virus has been important for analyzing its assembly, as described in an accompanying paper.

Capsid↗
PubMed1986

Modulation of humoral response to a 12-amino-acid site on the poliovirus virion.

Most monoclonal antibodies to poliovirus 3 but not poliovirus 1 require a single 12-amino-acid sequence in virion protein VP1 for neutralization (site 1). None of the available monoclonal antibodies requiring this site bound virions after tryptic cleavage of site 1. This result allowed the amount of site 1-specific antibodies to be determined in an antiserum by comparing its reactivity with virus and trypsin-cleaved virus. Antisera to poliovirus 3 Sabin strain (PS3) but not poliovirus 1 Sabin showed site 1 immunodominance, consistent with the frequency of isolation of site 1-specific monoclonal antibodies to these viruses. Cleavage of site 1 prior to immunization dramatically reduced the immunogenicity of this site in PS3. However, the antiserum against trypsin-cleaved PS3 still had a high neutralization titer, demonstrating that sites other than site 1 can elicit a neutralizing response to PS3. Other antisera to PS3 showed significant variability in the response to site 1, indicating that other factors, such as the genetic background of inbred mouse strains, the species immunized, and the immunization protocol, also affect immunodominance. In particular, a serum from a human infant recently immunized with oral trivalent vaccine had little response to site 1.

Amino Acid Sequence↗
PubMed1985

Three-dimensional structure of poliovirus at 2.9 A resolution.

The three-dimensional structure of poliovirus has been determined at 2.9 A resolution by x-ray crystallographic methods. Each of the three major capsid proteins (VP1, VP2, and VP3) contains a "core" consisting of an eight-stranded antiparallel beta barrel with two flanking helices. The arrangement of beta strands and helices is structurally similar and topologically identical to the folding pattern of the capsid proteins of several icosahedral plant viruses. In each of the major capsid proteins, the "connecting loops" and NH2- and COOH-terminal extensions are structurally dissimilar. The packing of the subunit "cores" to form the virion shell is reminiscent of the packing in the T = 3 plant viruses, but is significantly different in detail. Differences in the orientations of the subunits cause dissimilar contacts at protein-protein interfaces, and are also responsible for two major surface features of the poliovirion: prominent peaks at the fivefold and threefold axes of the particle. The positions and interactions of the NH2- and COOH-terminal strands of the capsid proteins have important implications for virion assembly. Several of the "connecting loops" and COOH-terminal strands form prominent radial projections which are the antigenic sites of the virion.

Amino Acid Sequence↗
PubMed1985

Trypsin sensitivity of the Sabin strain of type 1 poliovirus: cleavage sites in virions and related particles.

Treatment of the Sabin strain of type 1 poliovirus with trypsin produced two stable fragments of capsid protein VP1 which remained associated with the virions. Trypsinized virus was fully infectious and was neutralized by type-specific antisera. The susceptible site in the Sabin 1 strain was between the lysine at position 99 and the asparagine at position 100. A similar tryptic cleavage occurred in the Leon and Sabin strains of type 3 poliovirus, probably at the arginine at position 100, but not in the type 1 Mahoney strain, which lacks a basic residue at either position 99 or position 100. Tryptic treatment of heat-treated virus and 14S assembly intermediates produced unique stable fragments which were different from those produced in virions. The implications of our results for future characterization of the surface structures of these particles and structural rearrangements in the poliovirus capsid are discussed.

Hydrogen-Ion Concentration↗
PubMed1983

Generation of protein-reactive antibodies by short peptides is an event of high frequency: implications for the structural basis of immune recognition.

Recent studies have shown that chemically synthesized small peptides can induce antibodies that often react with intact proteins regardless of their position in the folded molecule. These findings are difficult to explain in view of the experimental and theoretical data which suggest that in the absence of forces provided by the folded protein, small peptides in aqueous solution do not readily adopt stable structures. In order to rationalize the two findings, there has been general acceptance of a stochastic model which suggests that the multiple conformers of a peptide in solution induce sets of antibodies with a small percentage reactive with conformations shared by the folded protein. This stochastic model has become less tenable as the success rate for the generation of protein-reactive anti-peptide antibodies has grown. To test the stochastic model, we have used monoclonal anti-peptide antibodies as a way of estimating the frequency with which small peptides induce antibodies that react with folded proteins. We have made monoclonal antibodies to six chemically synthesized peptides from three proteins. The frequency with which the peptides induce protein-reactive antibodies is at least 4 orders of magnitude greater than expected from previous experimental work and vastly different from what would be predicted by calculating the possible number of peptide conformers in solution. These findings make the stochastic model less likely and lead to consideration of other models. Aside from their practical significance for generation of highly specific reagents, these findings may have important implications for the protein folding problem.

Amino Acid Sequence↗
PubMedDate not supplied

Myristylation of picornavirus capsid protein VP4 and its structural significance.

We have obtained evidence that poliovirus and other picornavirus particles are specifically modified by having myristic acid covalently bound to a capsid protein. The electron density map of poliovirus confirms the position of the myristate molecule and defines its location in the virus particle. Analogies with other myristylated proteins suggest that the myristate moiety in picornaviruses may be involved in capsid assembly or in the entry of virus into cells.

Capsid↗