scholarly journals Discrimination among Rhinovirus Serotypes for a Variant ICAM-1 Receptor Molecule

2004 ◽  
Vol 78 (18) ◽  
pp. 10034-10044 ◽  
Author(s):  
Chuan Xiao ◽  
Tobias J. Tuthill ◽  
Carol M. Bator Kelly ◽  
Lisa J. Challinor ◽  
Paul R. Chipman ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Salt Bridge ◽  
Human Rhinovirus ◽  
Intercellular Adhesion Molecule ◽  
Stable Complex ◽  
Intercellular Adhesion Molecule 1 ◽  
Binding Characteristics ◽  
X Ray Crystallography ◽  
Density Maps ◽  
Charge Interaction

ABSTRACT Intercellular adhesion molecule 1 (ICAM-1) is the cellular receptor for the major group of human rhinovirus serotypes, including human rhinovirus 14 (HRV14) and HRV16. A naturally occurring variant of ICAM-1, ICAM-1Kilifi, has altered binding characteristics with respect to different HRV serotypes. HRV14 binds to ICAM-1 only transiently at physiological temperatures but forms a stable complex with ICAM-1Kilifi. Conversely, HRV16 forms a stable complex with ICAM-1 but does not bind to ICAM-1Kilifi. The three-dimensional structures of HRV14 and HRV16, complexed with ICAM-1, and the structure of HRV14, complexed with ICAM-1Kilifi, have been determined by cryoelectron microscopy (cryoEM) image reconstruction to a resolution of approximately 10 Å. Structures determined by X-ray crystallography of both viruses and of ICAM-1 were fitted into the cryoEM density maps. The interfaces between the viruses and receptors contain extensive ionic networks. However, the interactions between the viruses and ICAM-1Kilifi contain one less salt bridge than between the viruses and ICAM-1. As HRV16 has fewer overall interactions with ICAM-1 than HRV14, the absence of this charge interaction has a greater impact on the binding of ICAM-1Kilifi to HRV16 than to HRV14.

Cryoelectron microscopy of complexes of human rhinovirus with a monoclonal FAB and the viral cellular receptor

1992 ◽  
Vol 50 (1) ◽  
pp. 524-525
Author(s):  
Norman H. Olson ◽  
Thomas J. Smith ◽  
Prasanna R. Kolatkar ◽  
Marcos A. Oliveira ◽  
Roland R. Rueckert ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Antibody Fragment ◽  
Human Rhinovirus ◽  
Dimensional Structure ◽  
Intercellular Adhesion Molecule ◽  
Cellular Receptor ◽  
Intercellular Adhesion Molecule 1 ◽  
Amino Terminal ◽  
Functional Relationships ◽  
Neutralizing Monoclonal Antibody

Cryo-electron microscopy and image analysis techniques make it possible to study structural and functional relationships of macromolecular complexes that currently are not easily examined with crystallographic techniques. We have recorded images of frozen-hydrated human rhinovirus serotype-14 (HRV-14) complexed with a neutralizing, monoclonal, antibody fragment (Fab-17Ia; Fig. 1 A); and HRV-16 complexed with the amino-terminal, two-domain fragment (D1D2) of its cellular receptor (intercellular adhesion molecule-1, ICAM-1; Fig. 1B). Three-dimensional reconstructions (Figs. 2A,B) were calculated to ∽3nm resolution from 35 and 44 images of each complex, respectively. The HRV-14/Fab structure clearly identified the footprint of the Fab on the surface of the virion. The HRV-16/D1D2 reconstruction presents, for the first time, the three-dimensional structure of a complete virus complexed with its cellular receptor.

scholarly journals Antibody-Mediated Neutralization of Human Rhinovirus 14 Explored by Means of Cryoelectron Microscopy and X-Ray Crystallography of Virus-Fab Complexes

1998 ◽  
Vol 72 (6) ◽  
pp. 4610-4622 ◽  
Author(s):  
Zhiwei Che ◽  
Norman H. Olson ◽  
Donna Leippe ◽  
Wai-ming Lee ◽  
Anne G. Mosser ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Significant Proportion ◽  
Human Rhinovirus ◽  
Intercellular Adhesion Molecule ◽  
Cryoelectron Microscopy ◽  
Intercellular Adhesion Molecule 1 ◽  
Sequence Comparisons ◽  
X Ray ◽  
X Ray Crystallography ◽  
South Wall

ABSTRACT The structures of three different human rhinovirus 14 (HRV14)-Fab complexes have been explored with X-ray crystallography and cryoelectron microscopy procedures. All three antibodies bind to the NIm-IA site of HRV14, which is the β-B–β-C loop of the viral capsid protein VP1. Two antibodies, Fab17-IA (Fab17) and Fab12-IA (Fab12), bind bivalently to the virion surface and strongly neutralize viral infectivity whereas Fab1-IA (Fab1) strongly aggregates and weakly neutralizes virions. The structures of the two classes of virion-Fab complexes clearly differ and correlate with observed binding neutralization differences. Fab17 and Fab12 bind in essentially identical, tangential orientations to the viral surface, which favors bidentate binding over icosahedral twofold axes. Fab1 binds in a more radial orientation that makes bidentate binding unlikely. Although the binding orientations of these two antibody groups differ, nearly identical charge interactions occur at all paratope-epitope interfaces. Nucleotide sequence comparisons suggest that Fab17 and Fab12 are from the same progenitor cell and that some of the differing residues contact the south wall of the receptor binding canyon that encircles each of the icosahedral fivefold vertices. All of the antibodies contact a significant proportion of the canyon region and directly overlap much of the receptor (intercellular adhesion molecule 1 [ICAM-1]) binding site. Fab1, however, does not contact the same residues on the upper south wall (the side facing away from fivefold axes) at the receptor binding region as do Fab12 and Fab17. All three antibodies cause some stabilization of HRV14 against pH-induced inactivation; thus, stabilization may be mediated by invariant contacts with the canyon.

In vitro Inhibitory Activity of Soluble ICAM-1 for the Numbered Serotypes of Human Rhinovirus

1993 ◽  
Vol 4 (6) ◽  
pp. 323-327 ◽  
Author(s):  
C. E. Crump ◽  
E. Arruda ◽  
F. G. Hayden
Keyword(s):  
Human Rhinovirus ◽  
Intercellular Adhesion Molecule ◽  
Yield Reduction ◽  
Inhibitory Effects ◽  
Intercellular Adhesion Molecule 1 ◽  
Human Embryonic Lung ◽  
Group Type ◽  
Hel Cells ◽  
Soluble Intercellular Adhesion Molecule

We studied the antirhinovirus activity of soluble intercellular adhesion molecule-1 (sICAM-1) against all 100 numbered human rhinovirus (HRV) serotypes in human embryonic lung fibroblast (HEL) cells. sICAM-1 inhibited replication of 88 of 90 HRVs belonging to the major receptor group with 50% effective concentrations (EC50) ranging from 0.1 to 41.1 μg ml−1 (~0.002 to 0.8 μM). No inhibition at 100 μg ml−1 (~2 μM) was observed for HRV belonging to the minor receptor group, type 87, and two serotypes of the major receptor group (types 23 and 25). Yield reduction assays done with five HRV serotypes in human adenoid expiants found that sICAM-1 had concentration-dependent inhibitory effects that correlated closely with the activity observed in HEL cells ( r2 = 0.99, P < 0.001).

scholarly journals Molecular interaction mechanism of a 14-3-3 protein with a phosphorylated peptide elucidated by enhanced conformational sampling

2020 ◽  
Author(s):  
Junichi Higo ◽  
Takeshi Kawabata ◽  
Ayumi Kusaka ◽  
Kota Kasahara ◽  
Narutoshi Kamiya ◽  
...  
Keyword(s):  
Complex Structure ◽  
Three Dimensional ◽  
Interaction Mechanism ◽  
Salt Bridge ◽  
High Density ◽  
Receptor Protein ◽  
Stable Complex ◽  
Conformational Sampling ◽  
Stable Clusters ◽  
Phosphorylated Peptide

ABSTRACTEnhanced conformational sampling, a genetic-algorithm-guided multi-dimensional virtual-system coupled molecular dynamics, can provide equilibrated conformational distributions of a receptor protein and a flexible ligand at room temperature. The distributions provide not only the most stable but also semi-stable complex structures, and propose a ligand–receptor binding process. This method was applied to a system consisting of a receptor protein, 14-3-3ε, and a flexible peptide, phosphorylated Myeloid leukemia factor 1 (pMLF1). The results present comprehensive binding pathways of pMLF1 to 14-3-3ε. We identified four thermodynamically stable clusters of MLF1 on the 14-3-3ε surface, and free-energy barriers among some clusters. The most stable cluster includes two high-density spots connected by a narrow corridor. When pMLF1 passes the corridor, a salt-bridge relay (switching) related to the phosphorylated residue of pMLF1 occurs. Conformations in one high-density spots are similar to the experimentally determined complex structure. Three-dimensional distributions of residues in the intermolecular interface rationally explain the binding-constant changes resultant from alanine–mutation experiment for the residues. We performed a simulation of non-phosphorylated peptide and 14-3-3ε, which demonstrated that the complex structure was unstable, suggesting that phosphorylation of the peptide is crucially important for binding to 14-3-3ε.

scholarly journals Key Proteins Involved in Spheroid Formation and Angiogenesis in Endothelial Cells After Long-Term Exposure to Simulated Microgravity

2018 ◽  
Vol 45 (2) ◽  
pp. 429-445 ◽  
Author(s):  
Anita Dittrich ◽  
Daniela Grimm ◽  
Jayashree Sahana ◽  
Johann Bauer ◽  
Marcus Krüger ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecule ◽  
Cell Structure ◽  
Three Dimensional ◽  
Cardiovascular Complications ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Multicellular Spheroids ◽  
Monocyte Chemoattractant Protein 1 ◽  
Molecular Approaches

Background/Aims: Cardiovascular complications are common in astronauts returning from a prolonged spaceflight. These health problems might be driven by complex modulations of gene expression and protein synthesis in endothelial cells (ECs). Studies on the influence of microgravity on phenotype, growth pattern and biological processes of ECs can help to understand these complications. Methods: We exposed ECs (EA.hy926) to a Random Positioning Machine (RPM). Proteins associated with cell structure, angiogenesis and endothelial dysfunction were investigated in distinct pools of multicellular spheroids (MCS), adherent cells (AD) and tubular structures (TS) formed after a 35-day RPM-exposure. Results: Combining morphological and molecular approaches, we found AD, MCS and TS with changes in the synthesis and release of proteins involved in three-dimensional growth. Fibronectin and monocyte chemoattractant protein-1 (MCP-1) mRNAs and protein contents were elevated along with an increased secretion of vascular endothelial growth factor (VEGF), interleukin (IL)-6, IL-8, MCP-1, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), neutrophil gelatinase-associated lipocalin (NGAL) and regulated on activation, normal T cell expressed and secreted (RANTES) proteins in the culture supernatant as determined by multianalyte profiling technology. Together they form a network of interaction. Conclusions: These results show that a prolonged RPM-exposure of ECs induced TS and MCS formation. The factors VEGF, NGAL, IL-6, IL-8, MCP-1, VCAM-1, ICAM-1, fibronectin and RANTES seem to be affected when gravity is omitted.

Three-dimensional structure and ligand-binding site of carp fishelectin (FEL)

2015 ◽  
Vol 71 (5) ◽  
pp. 1123-1135 ◽  
Author(s):  
Stefano Capaldi ◽  
Beniamino Faggion ◽  
Maria E. Carrizo ◽  
Laura Destefanis ◽  
Maria C. Gonzalez ◽  
...  
Keyword(s):  
Amino Acid ◽  
Ligand Binding ◽  
Three Dimensional ◽  
Biochemical Properties ◽  
Amino Acid Sequences ◽  
Dimensional Structure ◽  
X Ray Crystallography ◽  
Homologous Genes ◽  
Density Maps ◽  
Conserved Water Molecules

Carp FEL (fishelectin or fish-egg lectin) is a 238-amino-acid lectin that can be purified from fish eggs by exploiting its selective binding to Sepharose followed by elution withN-acetylglucosamine. Its amino-acid sequence and other biochemical properties have previously been reported. The glycoprotein has four disulfide bridges and the structure of the oligosaccharides linked to Asn27 has been described. Here, the three-dimensional structures of apo carp FEL (cFEL) and of its complex withN-acetylglucosamine determined by X-ray crystallography at resolutions of 1.35 and 1.70 Å, respectively, are reported. The molecule folds as a six-bladed β-propeller and internal short consensus amino-acid sequences have been identified in all of the blades. A calcium atom binds at the bottom of the funnel-shaped tunnel located in the centre of the propeller. Two ligand-binding sites, α and β, are present in each of the two protomers in the dimer. The first site, α, is closer to the N-terminus of the chain and is located in the crevice between the second and the third blades, while the second site, β, is located between the fourth and the fifth blades. The amino acids that participate in the contacts have been identified, as well as the conserved water molecules in all of the sites. Both sites can bind the two anomers, α and β, ofN-acetylglucosamine, as is clearly recognizable in the electron-density maps. The lectin presents sequence homology to members of the tachylectin family, which are known to have a function in the innate immune system of arthropods, and homologous genes are present in the genomes of other fish and amphibians. This structure is the first of a protein of this group and, given the degree of homology with other members of the family, it is expected that it will be useful to experimentally determine other crystal structures using the coordinates of cFEL as a search probe in molecular replacement.

Instrumentation in X-ray crystallography: Past, present and future

2001 ◽  
Vol 55 (3) ◽  
pp. 457-472 ◽  
Author(s):  
U. W. Arndt
Keyword(s):  
Synchrotron Radiation ◽  
Three Dimensional ◽  
Macromolecular Crystallography ◽  
Personal Account ◽  
New Techniques ◽  
X Ray ◽  
X Ray Crystallography ◽  
Density Maps ◽  
Structure Determinations ◽  
Complete Automation

This paper deals with the very great changes in X–ray crystallographic techniques and apparatus over a period of approximately the last 60 years. This is not a general history; it is a personal account of the developments with which I have been directly involved; it is, therefore, biased towards apparatus developments in the field of macromolecular crystallography in which I have worked during most of this period. The bias needs little excuse: many of the new techniques of X–ray crystallography were devised initially for large–molecule structure determinations which had most need of such advances in order to be feasible at all. Among them are the uses of computers in calculating electron density maps, the construction of automatic diffractometers and microdensitometers, the introduction of rotating-anode X–ray generators and of microfocus X–ray tubes, the development of electronic X–ray area detectors, the pioneering work on the use of synchrotron radiation for diffraction studies, the building of three–dimensional atomic models by computer and the complete automation of the mounting, selection and alignment of crystals on the diffractometer.

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