scholarly journals Geometric constraints dominate the antigenic evolution of influenza H3N2 hemagglutinin

2015 ◽  
Author(s):  
Austin G Meyer ◽  
Claus O Wilke
Keyword(s):  
Receptor Binding ◽  
Protein Function ◽  
Influenza A ◽  
Immune Escape ◽  
Solvent Accessibility ◽  
Geometric Constraints ◽  
Binding Region ◽  
Primary Determinant ◽  
Evolutionary Variation ◽  
Receptor Binding Region

We have carried out a comprehensive analysis of the determinants of human influenza A H3 hemagglutinin evolution, considering three distinct predictors of evolutionary variation at individual sites: solvent accessibility (as a proxy for protein fold stability and/or conservation), experimental epitope sites (as a proxy for host immune bias), and proximity to the receptor-binding region (as a proxy for protein function). We found that these three predictors individually explain approximately 15% of the variation in site-wise dN/dS. The solvent accessibility and proximity predictors were largely independent of each other, while the epitope sites were not. In combination, solvent accessibility and proximity explained 32% of the variation in dN/dS. Incorporating experimental epitope sites into the model added only an additional 2 percentage points. We also found that the historical H3 epitope sites, which date back to the 1980s and 1990s, showed only weak overlap with the latest experimental epitope data. Finally, sites with dN/dS>1, i.e., the sites most likely driving seasonal immune escape, are not correctly predicted by either historical or experimental epitope sites, but only by proximity to the receptor-binding region. In summary, proximity to the receptor-binding region, and not host immune bias, seems to be the primary determinant of H3 evolution.

scholarly journals Amino acid polymorphism at residue 222 of the receptor-binding site of the hemagglutinin of the pandemic influenza A(H1N1)pdm09 from patients 166 with lethal virus pneumonia in 2012-2014

2016 ◽  
Vol 61 (4) ◽  
pp. 166-171 ◽  
Author(s):  
K. G. Krasnoslobodtsev ◽  
D. K. Lvov ◽  
S. V. Alkhovsky ◽  
E. I. Burtseva ◽  
I. T. Fedyakina ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Receptor Binding ◽  
Lower Respiratory Tract ◽  
Influenza A ◽  
Viral Population ◽  
Wild Type ◽  
Binding Region ◽  
Influenza A H1n1 ◽  
Mutant Forms ◽  
Receptor Binding Region

Survey data from autopsy specimens from patients who died from pneumonia caused by the influenza A(H1N1) pdm09 in 2012-2014 and mutant forms of influenza virus in these patients (position 222 in the receptor-binding region of hemagglutinin) were presented. In total, according to aggregate data, obtained with three different methods (sequencing, next-generation sequencing (NGS), virus isolation) mutant viruses were detected in 17 (41%) from 41 patients. The proportion of the mutant forms in viral populations ranged from 1% to 69.2%. The most frequent mixture was the wild type (D222) and mutant (D222G), with proportion of mutant type ranged from 3.3% to 69.2% in the viral population. Mutation D222N (from 1.1% to 5.5%) was found rarely. Composition of the viral population from one patient is extremely heterogeneous: in left lung there was only wild type D222, meantime in right lung - mixture of mutant forms 222D/N/G (65.4/32.5/1.1%), in trachea - mixture 222D/G/Y/A (61.8/35.6/1.2/1.4%, respectively), and in bronchi compound of 222D/G/N/A (64.3/33.7/1/1%, respectively) were detected. The obtained data indicate that the process of adaptation of the virus in the lower respiratory tract is coupled with the appearance of different virus variants with mutations in the receptor-binding region. Mutant forms of the virus are observed in the lower respiratory tract of the majority of patients with lethal viral pneumonia. However, if they are a minor part of the population, they cannot be detected by the method of conventional sequencing. They can be identified using the NGS methods.

scholarly journals A Receptor-binding Region inEscherichia coliα-Haemolysin

2003 ◽  
Vol 278 (21) ◽  
pp. 19159-19163 ◽  
Author(s):  
Aitziber L. Cortajarena ◽  
Félix M. Goñi ◽  
Helena Ostolaza
Keyword(s):  
Receptor Binding ◽  
Binding Region ◽  
Receptor Binding Region

The Galactosyl Ceramide/Sulfatide Receptor Binding Region of HIV-1 gp120 Maps to Amino Acids 206-275

1993 ◽  
Vol 9 (2) ◽  
pp. 175-181 ◽  
Author(s):  
SHAMA BHAT ◽  
RICHARD V. METTUS ◽  
E. PREMKUMAR REDDY ◽  
K.E. UGEN ◽  
V. SRIKANTHAN ◽  
...  
Keyword(s):  
Amino Acids ◽  
Receptor Binding ◽  
Binding Region ◽  
Galactosyl Ceramide ◽  
Receptor Binding Region ◽  
Hiv 1

Characterization of a complex glucocorticoid response unit in the phosphoenolpyruvate carboxykinase gene

1990 ◽  
Vol 10 (9) ◽  
pp. 4712-4719
Author(s):  
E Imai ◽  
P E Stromstedt ◽  
P G Quinn ◽  
J Carlstedt-Duke ◽  
J A Gustafsson ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Receptor Binding ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Binding Region ◽  
Factor Binding ◽  
Response Unit ◽  
Accessory Factor ◽  
Glucocorticoid Response ◽  
Glucocorticoid Induction ◽  
Receptor Binding Region

The minimal DNA sequence required for glucocorticoid induction of the phosphoenolpyruvate carboxykinase (PEPCK) gene in H4IIE rat hepatoma cells was defined. This novel glucocorticoid response unit (GRU) spans about 110 base pairs (bp) and includes two receptor-binding elements plus two accessory factor-binding elements. Purified glucocorticoid receptor bound to two regions (GR1 and GR2) between -395 and -349 bp relative to the transcription start site. Factors in crude rat liver nuclear extract bound to DNA in the regions -455 to -431 and -420 to -403 bp, which are designated accessory factor 1 (AF1) and accessory factor 2 (AF2) elements, respectively. Gel retardation analysis revealed that at least two proteins bound to AF1 and that they were distinct from the protein(s) that bound to AF2. Various combinations of GR1, GR2, AF1, and AF2 were fused to the chloramphenicol acetyltransferase (CAT) reporter gene and cotransfected with a glucocorticoid receptor expression plasmid (pSVGR1) into H4IIE cells to identify the functional GRU. Neither the glucocorticoid receptor binding region nor the accessory factor binding region alone was sufficient to confer glucocorticoid responsiveness. The two components of the glucocorticoid receptor binding region functioned independently, and each accounted for half of the maximal response, provided the accessory factor elements were present. Similarly, deletion of either AF1 or AF2 diminished glucocorticoid induction of the PEPCK gene to approximately half of the maximum. We propose that the complex PEPCK gene GRU provides the stringent regulation required of this critical enzyme in liver.

Rat relaxin: insulin-like fold predicts a likely receptor binding region

1982 ◽  
Vol 4 (7) ◽  
pp. 399-405 ◽  
Author(s):  
G.G. Dodson ◽  
E.E. Eliopoulos ◽  
N.W. Isaacs ◽  
M.J. McCall ◽  
H.D. Niall ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Binding Region ◽  
Receptor Binding Region

Bioactivities and Secondary Structures of Constrained Analogues of Human Parathyroid Hormone:  Cyclic Lactams of the Receptor Binding Region†

1997 ◽  
Vol 40 (9) ◽  
pp. 1373-1380 ◽  
Author(s):  
Jean-René Barbier ◽  
Witold Neugebauer ◽  
Paul Morley ◽  
Virginia Ross ◽  
Mark Soska ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Receptor Binding ◽  
Secondary Structures ◽  
Human Parathyroid Hormone ◽  
Binding Region ◽  
Receptor Binding Region
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