scholarly journals Conformational Dynamics of Nonenveloped Circovirus Capsid to the Host Cell Receptor

2019 ◽  
Author(s):  
Jiarong Li ◽  
Jinyan Gu ◽  
Shengnan Wang ◽  
Cui Lin ◽  
Jianwei Zhou ◽  
...  
Keyword(s):  
Cell Surface ◽  
Receptor Binding ◽  
Conformational Changes ◽  
Neutralizing Antibodies ◽  
Dynamic Equilibrium ◽  
Conformational Dynamics ◽  
Cell Surface Receptor ◽  
Virus Infectivity ◽  
Surface Receptor ◽  
Nonenveloped Virus

AbstractCircovirus, comprising one capsid protein, is the smallest nonenveloped virus and induces lymphopenia. Circovirus can be used to explore the cell adhesion mechanism of nonenveloped viruses. We developed a single-molecule fluorescence resonance energy transfer (smFRET) assay to directly visualize the capsid’s conformational feature. The capsid underwent reversible dynamic transformation between three conformations. The cell surface receptor heparan sulfate (HS) altered the dynamic equilibrium of the capsid to the high-FRET state, revealing the HS binding region. Neutralizing antibodies restricted capsid transition to a low-FRET state, masking the HS binding domain. The lack of positively charged amino acids in the HS binding site reduced cell surface affinity and attenuated virus infectivity via conformational changes. These intrinsic characteristics of the capsid suggested that conformational dynamics is critical for the structural changes occurring upon cell surface receptor binding, supporting a dynamics-based mechanism of receptor binding.ImportanceViral proteins were commom working as ligand to interacte with cell surface glycosaminoglycan receptors to achieve the virus attachment, during which the conformational dynamics of the protein ligand are also vital for the binding properties. In this study, PCV2 capsid and heparin sulfate were used to study the protein conformational dynamics of nonenveloped and icosahedral circovirus capsid during triggering to cell surface receptor. we demonstrated the PCV2 capsid could acts as a dynamic machine, spontaneously adopting multiple conformations with reversible interconversion and intrinsic conformational features could be regulated by glycosaminoglycan receptors and neutralizing antibodies. These increased our understanding of the mechanism by which nonenveloped virus attach to cells.

scholarly journals Nectin-Like Interactions between Poliovirus and Its Receptor Trigger Conformational Changes Associated with Cell Entry

2015 ◽  
Vol 89 (8) ◽  
pp. 4143-4157 ◽  
Author(s):  
Mike Strauss ◽  
David J. Filman ◽  
David M. Belnap ◽  
Naiqian Cheng ◽  
Roane T. Noel ◽  
...  
Keyword(s):  
Cell Surface ◽  
Capsid Protein ◽  
Receptor Binding ◽  
Conformational Changes ◽  
Three Dimensional ◽  
Cell Surface Receptor ◽  
Membrane Structures ◽  
Lipid Molecule ◽  
Surface Receptor ◽  
Capsid Protein Vp1

ABSTRACTPoliovirus infection is initiated by attachment to a receptor on the cell surface called Pvr or CD155. At physiological temperatures, the receptor catalyzes an irreversible expansion of the virus to form an expanded form of the capsid called the 135S particle. This expansion results in the externalization of the myristoylated capsid protein VP4 and the N-terminal extension of the capsid protein VP1, both of which become inserted into the cell membrane. Structures of the expanded forms of poliovirus and of several related viruses have recently been reported. However, until now, it has been unclear how receptor binding triggers viral expansion at physiological temperature. Here, we report poliovirus in complex with an enzymatically partially deglycosylated form of the 3-domain ectodomain of Pvr at a 4-Å resolution, as determined by cryo-electron microscopy. The interaction of the receptor with the virus in this structure is reminiscent of the interactions of Pvr with its natural ligands. At a low temperature, the receptor induces very few changes in the structure of the virus, with the largest changes occurring within the footprint of the receptor, and in a loop of the internal protein VP4. Changes in the vicinity of the receptor include the displacement of a natural lipid ligand (called “pocket factor”), demonstrating that the loss of this ligand, alone, is not sufficient to induce particle expansion. Finally, analogies with naturally occurring ligand binding in the nectin family suggest which specific structural rearrangements in the virus-receptor complex could help to trigger the irreversible expansion of the capsid.IMPORTANCEThe cell-surface receptor (Pvr) catalyzes a large structural change in the virus that exposes membrane-binding protein chains. We fitted known atomic models of the virus and Pvr into three-dimensional experimental maps of the receptor-virus complex. The molecular interactions we see between poliovirus and its receptor are reminiscent of the nectin family, by involving the burying of otherwise-exposed hydrophobic groups. Importantly, poliovirus expansion is regulated by the binding of a lipid molecule within the viral capsid. We show that receptor binding either causes this molecule to be expelled or requires it, but that its loss is not sufficient to trigger irreversible expansion. Based on our model, we propose testable hypotheses to explain how the viral shell becomes destabilized, leading to RNA uncoating. These findings give us a better understanding of how poliovirus has evolved to exploit a natural process of its host to penetrate the membrane barrier.

scholarly journals Specific Capture of Mammalian Cells by Cell Surface Receptor Binding to Ligand Immobilized on Gold Thin Films

2006 ◽  
Vol 5 (7) ◽  
pp. 1580-1585 ◽  
Author(s):  
Dora Peelen ◽  
Voula Kodoyianni ◽  
Jieun Lee ◽  
Ting Zheng ◽  
Michael R. Shortreed ◽  
...  
Keyword(s):  
Thin Films ◽  
Cell Surface ◽  
Receptor Binding ◽  
Mammalian Cells ◽  
Cell Surface Receptor ◽  
Surface Receptor ◽  
Gold Thin Films

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.

scholarly journals Factors That Increase the Effective Concentration of CXCR4 Dictate Feline Immunodeficiency Virus Tropism and Kinetics of Replication

2004 ◽  
Vol 78 (17) ◽  
pp. 9132-9143 ◽  
Author(s):  
Aymeric de Parseval ◽  
Stacie Ngo ◽  
Peiqing Sun ◽  
John H. Elder
Keyword(s):  
Cell Surface ◽  
Conformational Changes ◽  
Feline Immunodeficiency Virus ◽  
Effective Concentration ◽  
Surface Glycoprotein ◽  
Cell Surface Receptor ◽  
Productive Infection ◽  
Immunodeficiency Virus ◽  
Surface Receptor ◽  
Extensive Cell

ABSTRACT The surface glycoprotein (gp95) of the feline immunodeficiency virus (FIV) binds in a strain-specific manner to several cell surface molecules, including CXCR4, heparan sulfate proteoglycans (HSPGs), DC-SIGN, and a 43-kDa cell surface receptor on T cells recently identified as CD134 by M. Shimojima et al. (Science 303:1192-1195, 2004). CXCR4 is the entry receptor in all known cases, and the other molecules act as binding receptors to help facilitate infection. In this report, we confirm and extend the findings regarding CD134 as a primary receptor for FIV. In addition, we show that temperature critically influences the binding properties of FIV gp95 to CXCR4 and HSPGs. The data show that gp95 of the field strain FIV-PPR bound to CXCR4 at 22°C, whereas binding was not detected at 4°C. In contrast, binding of the laboratory adapted FIV-34TF10 gp95 was observed at either 4°C or 22°C, albeit at increased levels at the higher temperature. The level of CXCR4 increased after the temperature was switched from 4 to 22°C, whereas the level of HSPGs decreased, resulting in higher binding of gp95 from both strains to CXCR4 and lower binding of gp95 of FIV-34TF10 to HSPGs (FIV-PPR gp95 does not bind to these molecules). The findings also show that HSPGs facilitate the CXCR4-mediated infectivity of CrFK and G355-5 cells by FIV-34TF10. These two nonlymphoid cell lines express very low levels of CXCR4 and are permissive to FIV-34TF10 but not to productive infection by FIV-PPR. However, overexpression of human CXCR4 in CrFK or G-355-5 cells resulted in extensive cell fusion and infection by FIV-PPR. Taken together, these findings indicate that factors that increase the effective concentration of CXCR4 enhance FIV infectivity and may involve (i) temperature or ligand-induced conformational changes in CXCR4 that enhance SU binding, (ii) coreceptor interactions with gp95 that either alter gp95 conformation to enhance CXCR4 binding and/or raise the localized concentration of receptor or ligand, or (iii) direct increase in CXCR4 concentration via overexpression.

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