scholarly journals Sequence and Structure of Human Rhinoviruses Reveal the Basis of Receptor Discrimination

2003 ◽  
Vol 77 (12) ◽  
pp. 6923-6930 ◽  
Author(s):  
Marketa Vlasak ◽  
Soile Blomqvist ◽  
Tapani Hovi ◽  
Elizabeth Hewat ◽  
Dieter Blaas
Keyword(s):  
Low Density Lipoprotein ◽  
Three Dimensional ◽  
Density Lipoprotein ◽  
Major Group ◽  
Amino Acid Residues ◽  
X Ray ◽  
Vldl Receptor ◽  
Capsid Protein Vp1 ◽  
Three Dimensional Models ◽  
Positively Charged

ABSTRACT The sequences of the capsid protein VP1 of all minor receptor group human rhinoviruses were determined. A phylogenetic analysis revealed that minor group HRVs were not more related to each other than to the nine major group HRVs whose sequences are known. Examination of the surface exposed amino acid residues of HRV1A and HRV2, whose X-ray structures are available, and that of three-dimensional models computed for the remaining eight minor group HRVs indicated a pattern of positively charged residues within the region, which, in HRV2, was shown to be the binding site of the very-low-density lipoprotein (VLDL) receptor. A lysine in the HI loop of VP1 (K224 in HRV2) is strictly conserved within the minor group. It lies in the middle of the footprint of a single repeat of the VLDL receptor on HRV2. Major group virus serotypes exhibit mostly negative charges at the corresponding positions and do not bind the negatively charged VLDL receptor, presumably because of charge repulsion.

scholarly journals The Minor Receptor Group of Human Rhinovirus (HRV) Includes HRV23 and HRV25, but the Presence of a Lysine in the VP1 HI Loop Is Not Sufficient for Receptor Binding

2005 ◽  
Vol 79 (12) ◽  
pp. 7389-7395 ◽  
Author(s):  
Marketa Vlasak ◽  
Merja Roivainen ◽  
Manuela Reithmayer ◽  
Irene Goesler ◽  
Pia Laine ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Major Group ◽  
Intercellular Adhesion Molecule ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Intercellular Adhesion Molecule 1 ◽  
Low Density Lipoprotein Receptor ◽  
Density Lipoprotein Receptor ◽  
Capsid Protein Vp1

ABSTRACT Like all 10 minor receptor group human rhinoviruses (HRVs), HRV23 and HRV25, previously classified as major group viruses, are neutralized by maltose binding protein (MBP)-V33333 (a soluble recombinant concatemer of five copies of repeat 3 of the very-low-density lipoprotein receptor fused to MBP), bind to low-density lipoprotein receptor in virus overlay blots, and replicate in intercellular adhesion molecule 1 (ICAM-1)-negative COS-7 cells. From phylogenetic analysis of capsid protein VP1-coding sequences, they are also known to cluster together with other minor group strains. Therefore, they belong to the minor group; there are now 12 minor group and 87 major group HRV serotypes. Sequence comparison of the VP1 capsid proteins of all HRVs revealed that the lysine in the HI loop, strictly conserved in the 12 minor group HRVs, is also present in 9 major group serotypes that are neutralized by soluble ICAM-1. Despite the presence of this lysine, they are not neutralized by MBP-V33333 and fail to replicate in COS-7 cells and in HeLa cells in the presence of an ICAM-1-blocking antibody. These nine serotypes are therefore “true” major group viruses.

scholarly journals Improved scFv Anti-LOX-1 Binding Activity by Fusion with LOX-1-Binding Peptides

2017 ◽  
Vol 2017 ◽  
pp. 1-9
Author(s):  
Wei Hu ◽  
Qiuhong Xie ◽  
Hongyu Xiang
Keyword(s):  
Targeted Delivery ◽  
Structural Characteristics ◽  
Low Density Lipoprotein ◽  
Three Dimensional ◽  
Density Lipoprotein ◽  
Binding Activity ◽  
Single Chain ◽  
C Terminus ◽  
Density Lipoprotein Receptor ◽  
Therapeutic Molecules

The oxidized low-density lipoprotein receptor-1 (LOX-1) targeted single-chain variable fragment (scFvs) is a promising molecule for the targeted delivery of imaging and therapeutic molecules of atherosclerotic diseases; however, its applications are limited by the inherent low antigen affinity. In this study, the three-dimensional (3D) model of the anti-LOX-1 scFv was constructed and its docking with the LOX-1 protein was developed. To improve the LOX-1-binding activity, the anti-LOX-1 scFv was designed to fuse with one of three LOX-1-binding heptapeptides, LTPATAI, FQTPPQL, and LSIPPKA, at its N-terminus and C-terminus and in the linker region, which have different LOX-1-binding interfaces with the anti-LOX-1 scFv analyzed by an array of computational approaches. These scFv/peptide fusions were constructed, successfully expressed in Brevibacillus choshinensis hosts, and purified by a two-step column purification process. The antigen binding activity, structural characteristics, thermal stability, and stability in serum of these fusion proteins were examined. Results showed that the scFv with N-terminal fusing peptides proteins demonstrated increased LOX-1-binding activity without decrease in stability. These findings will help increase the application efficacy of LOX-1 targeting scFv in LOX-1-based therapy.

scholarly journals Combining Coherent Hard X-Ray Tomographies with Phase Retrieval to Generate Three-Dimensional Models of Forming Bone

2017 ◽  
Vol 4 ◽  
Author(s):  
Emely L. Bortel ◽  
Max Langer ◽  
Alexander Rack ◽  
Jean-Baptiste Forien ◽  
Georg N. Duda ◽  
...  
Keyword(s):  
Phase Retrieval ◽  
Three Dimensional ◽  
X Ray ◽  
Dimensional Models ◽  
Three Dimensional Models

scholarly journals Shear stress influences spatial variations in vascular Mn-SOD expression: implication for LDL nitration

2008 ◽  
Vol 294 (6) ◽  
pp. C1576-C1585 ◽  
Author(s):  
Lisong Ai ◽  
Mahsa Rouhanizadeh ◽  
Joseph C. Wu ◽  
Wakako Takabe ◽  
Hongyu Yu ◽  
...  
Keyword(s):  
Shear Stress ◽  
Manganese Superoxide Dismutase ◽  
Fluid Shear Stress ◽  
Low Density Lipoprotein ◽  
Three Dimensional ◽  
Density Lipoprotein ◽  
Static Condition ◽  
Lateral Wall ◽  
Spatial Variations ◽  
Arterial Bifurcation

Fluid shear stress modulates vascular production of endothelial superoxide anion (O2·−) and nitric oxide (·NO). Whether the characteristics of shear stress influence the spatial variations in mitochondrial manganese superoxide dismutase (Mn-SOD) expression in vasculatures is not well defined. We constructed a three-dimensional computational fluid dynamics model simulating spatial variations in shear stress at the arterial bifurcation. In parallel, explants of arterial bifurcations were sectioned from the human left main coronary bifurcation and right coronary arteries for immunohistolocalization of Mn-SOD expression. We demonstrated that Mn-SOD staining was prominent in the pulsatile shear stress (PSS)-exposed and atheroprotective regions, but it was nearly absent in the oscillatory shear stress (OSS)-exposed regions and lateral wall of arterial bifurcation. In cultured bovine aortic endothelial cells, PSS at mean shear stress (τave) of 23 dyn/cm2 upregulated Mn-SOD mRNA expression at a higher level than did OSS at τave = 0.02 dyn/cm2 ± 3.0 dyn·cm−2·s−1 and at 1 Hz (PSS by 11.3 ± 0.4-fold vs. OSS by 5.0 ± 0.5-fold vs. static condition; P < 0.05, n = 4). By liquid chromatography and tandem mass spectrometry, it was found that PSS decreased the extent of low-density lipoprotein (LDL) nitration, whereas OSS increased nitration ( P < 0.05, n = 4). In the presence of LDL, treatment with Mn-SOD small interfering RNA increased intracellular nitrotyrosine level ( P < 0.5, n = 4), a fingerprint for nitrotyrosine formation. Our findings indicate that shear stress in the atheroprone versus atheroprotective regions regulates spatial variations in mitochondrial Mn-SOD expression with an implication for modulating LDL nitration.

Natural History of Carotid Atherosclerosis in Relation to the Hemodynamic Environment

Angiology ◽  
2016 ◽  
Vol 68 (2) ◽  
pp. 109-118 ◽  
Author(s):  
Antonis I. Sakellarios ◽  
Paschalis Bizopoulos ◽  
Michail I. Papafaklis ◽  
Lambros Athanasiou ◽  
Themis Exarchos ◽  
...  
Keyword(s):  
Blood Flow ◽  
Natural History ◽  
Mass Transport ◽  
Carotid Atherosclerosis ◽  
Low Density Lipoprotein ◽  
Three Dimensional ◽  
Density Lipoprotein ◽  
Magnetic Resonance Data ◽  
History Of ◽  
Plaque Growth

Carotid atherosclerosis may lead to devastating clinical outcomes such as stroke. Data on the value of local factors in predicting progression in carotid atherosclerosis are limited. Our aim was to investigate the association of local endothelial shear stress (ESS) and low-density lipoprotein (LDL) accumulation with the natural history of atherosclerotic disease using a series of 3 time points of human magnetic resonance data. Three-dimensional lumen/wall reconstruction was performed in 12 carotids, and blood flow and LDL mass transport modeling were performed. Our results showed that an increase in plaque thickness and a decrease in lumen size were associated with low ESS and high LDL accumulation in the arterial wall. Low ESS (odds ratio [OR]: 2.99; 95% confidence interval [CI]: 2.31-3.88; P < .001 vs higher ESS) and high LDL concentration (OR: 3.26; 95% CI: 2.44-4.36; P < .001 vs higher LDL concentration) were significantly associated with substantial local plaque growth. Low ESS and high LDL accumulation both presented a diagnostic accuracy of 67% for predicting plaque growth regions. Modeling of blood flow and LDL mass transport show promise in predicting progression of carotid atherosclerosis.

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