scholarly journals Determination of the human type I interferon receptor binding site on human interferon-α2 by cross saturation and an NMR-based model of the complex

2006 ◽  
Vol 15 (11) ◽  
pp. 2656-2668 ◽  
Author(s):  
Sabine R. Quadt-Akabayov ◽  
Jordan H. Chill ◽  
Rina Levy ◽  
Naama Kessler ◽  
Jacob Anglister
Keyword(s):  
Binding Site ◽  
Receptor Binding ◽  
Type I Interferon ◽  
Human Interferon ◽  
Type I ◽  
Receptor Binding Site ◽  
Human Type ◽  
Interferon Receptor ◽  
Interferon Α2

Determination of the molecular size of the 5-HT3 receptor binding site by radiation inactivation

1989 ◽  
Vol 172 (6) ◽  
pp. 497-500 ◽  
Author(s):  
H. Gozlan ◽  
L.E. Schechter ◽  
F. Bolanos ◽  
M.B. Emerit ◽  
M.C. Miquel ◽  
...  
Keyword(s):  
Binding Site ◽  
Receptor Binding ◽  
Molecular Size ◽  
Receptor Binding Site ◽  
Radiation Inactivation

Human Type I Interferon Receptor, IFNAR, Is a Heavily Glycosylated 120-130 kD Membrane Protein

1995 ◽  
Vol 15 (1) ◽  
pp. 55-61 ◽  
Author(s):  
LEONA E. LING ◽  
MOHAMMAD ZAFARI ◽  
DONNA REARDON ◽  
MARGOT BRICKELMEIER ◽  
SUSAN E. GOELZ ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Type I Interferon ◽  
Type I ◽  
Human Type ◽  
Interferon Receptor

scholarly journals Phenotypic Effects of Substitutions within the Receptor Binding Site of Highly Pathogenic Avian Influenza H5N1 Virus Observed during Human Infection

2020 ◽  
Vol 94 (13) ◽  
Author(s):  
Dirk Eggink ◽  
Monique Spronken ◽  
Roosmarijn van der Woude ◽  
Jocynthe Buzink ◽  
Frederik Broszeit ◽  
...  
Keyword(s):  
Amino Acid ◽  
Avian Influenza ◽  
Binding Site ◽  
Receptor Binding ◽  
Human Infection ◽  
Influenza Viruses ◽  
Receptor Specificity ◽  
Receptor Binding Site ◽  
Human Type ◽  
Human Infections

ABSTRACT Highly pathogenic avian influenza (HPAI) viruses are enzootic in wild birds and poultry and continue to cause human infections with high mortality. To date, more than 850 confirmed human cases of H5N1 virus infection have been reported, of which ∼60% were fatal. Global concern persists that these or similar avian influenza viruses will evolve into viruses that can transmit efficiently between humans, causing a severe influenza pandemic. It was shown previously that a change in receptor specificity is a hallmark for adaptation to humans and evolution toward a transmittable virus. Substantial genetic diversity was detected within the receptor binding site of hemagglutinin of HPAI A/H5N1 viruses, evolved during human infection, as detected by next-generation sequencing. Here, we investigated the functional impact of substitutions that were detected during these human infections. Upon rescue of 21 mutant viruses, most substitutions in the receptor binding site (RBS) resulted in viable virus, but virus replication, entry, and stability were often impeded. None of the tested substitutions individually resulted in a clear switch in receptor preference as measured with modified red blood cells and glycan arrays. Although several combinations of the substitutions can lead to human-type receptor specificity, accumulation of multiple amino acid substitutions within a single hemagglutinin during human infection is rare, thus reducing the risk of virus adaptation to humans. IMPORTANCE H5 viruses continue to be a threat for public health. Because these viruses are immunologically novel to humans, they could spark a pandemic when adapted to transmit between humans. Avian influenza viruses need several adaptive mutations to bind to human-type receptors, increase hemagglutinin (HA) stability, and replicate in human cells. However, knowledge on adaptive mutations during human infections is limited. A previous study showed substantial diversity within the receptor binding site of H5N1 during human infection. We therefore analyzed the observed amino acid changes phenotypically in a diverse set of assays, including virus replication, stability, and receptor specificity. None of the tested substitutions resulted in a clear step toward a human-adapted virus capable of aerosol transmission. It is notable that acquiring human-type receptor specificity needs multiple amino acid mutations, and that variability at key position 226 is not tolerated, reducing the risk of them being acquired naturally.

Transcription Termination/Polyadenylation Occurs at Multiple Sites in the Human Type I Interferon Receptor Gene

1993 ◽  
Vol 13 (5) ◽  
pp. 329-332 ◽  
Author(s):  
LUCINDA L. HENSLEY ◽  
PATRICK J. VOJTA ◽  
VICTOR K.M. HAN ◽  
DAVID C. LEE ◽  
HOWARD OZER
Keyword(s):  
Type I Interferon ◽  
Transcription Termination ◽  
Receptor Gene ◽  
Type I ◽  
Human Type ◽  
Interferon Receptor

scholarly journals Role of the Intracellular Domain of the Human Type I Interferon Receptor 2 Chain (IFNAR2c) in Interferon Signaling

2000 ◽  
Vol 275 (31) ◽  
pp. 23981-23985 ◽  
Author(s):  
Dean Russell-Harde ◽  
T. Charis Wagner ◽  
M. R. Sandhya Rani ◽  
David Vogel ◽  
Oscar Colamonici ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Type I ◽  
Interferon Signaling ◽  
Intracellular Domain ◽  
Human Type ◽  
Interferon Receptor

scholarly journals Differential Responsiveness of a Splice Variant of the Human Type I Interferon Receptor to Interferons

1996 ◽  
Vol 271 (23) ◽  
pp. 13448-13453 ◽  
Author(s):  
Jeffry R. Cook ◽  
Cathleen M. Cleary ◽  
Thomas M. Mariano ◽  
Lara Izotova ◽  
Sidney Pestka
Keyword(s):  
Splice Variant ◽  
Type I Interferon ◽  
Type I ◽  
Human Type ◽  
Interferon Receptor ◽  
Differential Responsiveness

scholarly journals A Bone Morphogenetic Protein (BMP)-derived Peptide Based on the Type I Receptor-binding Site Modifies Cell-type Dependent BMP Signalling

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Zhen Tong ◽  
Jingxu Guo ◽  
Robert C. Glen ◽  
Nicholas W. Morrell ◽  
Wei Li
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Binding Site ◽  
Receptor Binding ◽  
Transforming Growth Factor ◽  
Alpha Helix ◽  
Type I ◽  
Cell Type ◽  
Receptor Binding Site ◽  
Baseline Activity

Abstract Bone morphogenetic proteins (BMPs) are multifunctional cytokines of the transforming growth factor β (TGFβ) superfamily with potential therapeutic applications due to their broad biological functionality. Designing BMP mimetics with specific activity will contribute to the translational potential of BMP-based therapies. Here, we report a BMP9 peptide mimetic, P3, designed from the type I receptor binding site, which showed millimolar binding affinities for the type I receptor activin receptor like kinase 1 (ALK1), ALK2 and ALK3. Although showing no baseline activity, P3 significantly enhanced BMP9-induced Smad1/5 phosphorylation as well as ID1, BMPR2, HEY1 and HEY2 gene expression in pulmonary artery endothelial cells (hPAECs), and this activity is dependent on its alpha helix propensity. However, in human dermal microvascular endothelial cells, P3 did not affect BMP9-induced Smad1/5 phosphorylation, but potently inhibited ALK3-dependent BMP4-induced Smad1/5 phosphorylation and gene expression. In C2C12 mouse myoblast cells, P3 had no effect on BMP9-induced osteogenic signalling, which is primarily mediated by ALK2. Interestingly, a previously published peptide from the knuckle region of BMP9 was found to inhibit BMP4-induced Smad1/5 phosphorylation. Together, our data identify a BMP9-derived peptide that can selectively enhance ALK1-mediated BMP9 signalling in hPAECs and modulate BMP9 and BMP4 signalling in a cell type-specific manner.

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