Structural basis of Nipah and Hendra virus attachment to their cell-surface receptor ephrin-B2

2008 ◽  
Vol 15 (6) ◽  
pp. 567-572 ◽  
Author(s):  
Thomas A Bowden ◽  
A Radu Aricescu ◽  
Robert J C Gilbert ◽  
Jonathan M Grimes ◽  
E Yvonne Jones ◽  
...  
Keyword(s):  
Cell Surface ◽  
Hendra Virus ◽  
Cell Surface Receptor ◽  
Structural Basis ◽  
Virus Attachment ◽  
Surface Receptor

Structural basis of cell surface receptor recognition by botulinum neurotoxin B

Nature ◽  
2006 ◽  
Vol 444 (7122) ◽  
pp. 1096-1100 ◽  
Author(s):  
Qing Chai ◽  
Joseph W. Arndt ◽  
Min Dong ◽  
William H. Tepp ◽  
Eric A. Johnson ◽  
...  
Keyword(s):  
Cell Surface ◽  
Botulinum Neurotoxin ◽  
Cell Surface Receptor ◽  
Structural Basis ◽  
Receptor Recognition ◽  
Surface Receptor ◽  
Botulinum Neurotoxin B

scholarly journals Structural basis for HCMV Pentamer recognition by antibodies and neuropilin 2

2021 ◽  
Author(s):  
Daniel Wrapp ◽  
Xiaohua Ye ◽  
Zhiqiang Ku ◽  
Hang Su ◽  
Harrison G Jones ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Surface ◽  
Neutralizing Antibodies ◽  
Cell Surface Receptor ◽  
Structural Basis ◽  
Calcium Dependent ◽  
High Affinity ◽  
Molecular Determinants ◽  
Surface Receptor ◽  
Affinity Interaction

Human cytomegalovirus (HCMV) encodes for multiple surface glycoproteins and glycoprotein complexes. One of these complexes, the HCMV Pentamer (gH, gL, UL128, UL130 and UL131), mediates tropism to both epithelial and endothelial cells by interacting with the cell surface receptor neuropilin 2 (NRP2). Despite the critical nature of this interaction, the molecular determinants that govern NRP2 recognition remain unclear. Here we describe the cryo-EM structure of NRP2 bound to the HCMV Pentamer. The high-affinity interaction between these proteins is calcium-dependent and differs from the canonical C-terminal arginine (CendR) binding that NRP2 typically utilizes. The interaction is primarily mediated by NRP2 domains a2 and b2, which interact with UL128 and UL131. We also determine the structures of four human-derived neutralizing antibodies in complex with the HCMV Pentamer to define susceptible epitopes. The two most potent antibodies recognize a novel epitope yet do not compete with NRP2 binding. Collectively, these findings provide a structural basis for HCMV tropism and antibody-mediated neutralization, and serve as a guide for the development of HCMV treatments and vaccines.

scholarly journals Molecular recognition of human ephrinB2 cell surface receptor by an emergent African henipavirus

2015 ◽  
Vol 112 (17) ◽  
pp. E2156-E2165 ◽  
Author(s):  
Benhur Lee ◽  
Olivier Pernet ◽  
Asim A. Ahmed ◽  
Antra Zeltina ◽  
Shannon M. Beaty ◽  
...  
Keyword(s):  
Cell Surface ◽  
Receptor Binding ◽  
Function Analysis ◽  
Cell Receptor ◽  
Hendra Virus ◽  
Cell Surface Receptor ◽  
Receptor Interaction ◽  
Human Populations ◽  
Evolutionary Constraint ◽  
Surface Receptor

The discovery of African henipaviruses (HNVs) related to pathogenic Hendra virus (HeV) and Nipah virus (NiV) from Southeast Asia and Australia presents an open-ended health risk. Cell receptor use by emerging African HNVs at the stage of host-cell entry is a key parameter when considering the potential for spillover and infection of human populations. The attachment glycoprotein from a Ghanaian bat isolate (GhV-G) exhibits <30% sequence identity with Asiatic NiV-G/HeV-G. Here, through functional and structural analysis of GhV-G, we show how this African HNV targets the same human cell-surface receptor (ephrinB2) as the Asiatic HNVs. We first characterized this virus−receptor interaction crystallographically. Compared with extant HNV-G–ephrinB2 structures, there was significant structural variation in the six-bladed β-propeller scaffold of the GhV-G receptor-binding domain, but not the Greek key fold of the bound ephrinB2. Analysis revealed a surprisingly conserved mode of ephrinB2 interaction that reflects an ongoing evolutionary constraint among geographically distal and phylogenetically divergent HNVs to maintain the functionality of ephrinB2 recognition during virus–host entry. Interestingly, unlike NiV-G/HeV-G, we could not detect binding of GhV-G to ephrinB3. Comparative structure–function analysis further revealed several distinguishing features of HNV-G function: a secondary ephrinB2 interaction site that contributes to more efficient ephrinB2-mediated entry in NiV-G relative to GhV-G and cognate residues at the very C terminus of GhV-G (absent in Asiatic HNV-Gs) that are vital for efficient receptor-induced fusion, but not receptor binding per se. These data provide molecular-level details for evaluating the likelihood of African HNVs to spill over into human populations.

Expression, function, and localization of the REG cell surface receptor

2001 ◽  
Vol 120 (5) ◽  
pp. A18-A19
Author(s):  
B DIECKGRAEFE ◽  
C HOUCHEN ◽  
H ZHANG
Keyword(s):  
Cell Surface ◽  
Cell Surface Receptor ◽  
Surface Receptor

Inhibition of rat ventricular automaticity by adenosine

1985 ◽  
Vol 248 (6) ◽  
pp. H907-H913 ◽  
Author(s):  
L. J. Heller ◽  
R. A. Olsson
Keyword(s):  
Cell Surface ◽  
Cell Surface Receptor ◽  
Chronotropic Effect ◽  
Surface Receptors ◽  
Adenosine Concentration ◽  
Surface Receptor ◽  
Ventricular Automaticity ◽  
Beating Rate ◽  
Chronotropic Effects ◽  
Developed Pressure

This study was designed to characterize adenosine's negative chronotropic effect on ventricular pacemakers. The spontaneous beating rate of isolated, isovolumic rat ventricular preparations perfused with Krebs-Henseleit solution decreased as the adenosine concentration was increased [log M effective concentration 50% (EC50) = -5.22 +/- 0.17]. The lack of effect of propranolol or atropine on this adenosine response eliminates the involvement of endogenous neurotransmitters. Support for the involvement of an external cell surface receptor was provided by findings that theophylline and 8-(4-sulfophenyl)theophylline, an analogue thought to act solely at the cell surface, significantly increased the adenosine log M EC50 to -3.94 +/- 0.22 and -3.61 +/- 0.22, respectively. An increase in spontaneous beating rate induced by theophylline, but not by its analogue, was blocked by the addition of propranolol. The relative chronotropic potency of the adenosine analogues R-PIA, S-PIA, and NECA suggests that the cell surface receptors may be of the Ri type. The negative chronotropic effects of adenosine and its analogues occurred at concentrations that had no effect on the developed pressure of the paced preparation. Electrocardiographic evaluations indicate that at high agonist concentrations, there was an abrupt alteration in electrical properties of the preparation, which could be blocked by theophylline and its analogue.

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