scholarly journals Chemoenzymatic Synthesis and Receptor Binding of Mannose-6-Phosphate (M6P)-Containing Glycoprotein Ligands Reveal Unusual Structural Requirements for M6P Receptor Recognition

2016 ◽  
Vol 138 (38) ◽  
pp. 12472-12485 ◽  
Author(s):  
Takahiro Yamaguchi ◽  
Mohammed N. Amin ◽  
Christian Toonstra ◽  
Lai-Xi Wang
Keyword(s):  
Receptor Binding ◽  
Chemoenzymatic Synthesis ◽  
Structural Requirements ◽  
Receptor Recognition ◽  
Mannose 6 Phosphate

scholarly journals Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen

2017 ◽  
Vol 114 (35) ◽  
pp. E7348-E7357 ◽  
Author(s):  
Jesper Pallesen ◽  
Nianshuang Wang ◽  
Kizzmekia S. Corbett ◽  
Daniel Wrapp ◽  
Robert N. Kirchdoerfer ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Case Fatality ◽  
Neutralizing Antibody ◽  
Human Populations ◽  
Receptor Binding Domain ◽  
Potential Mechanism ◽  
Primary Target ◽  
Humoral Immune ◽  
Receptor Recognition ◽  
Antibody Titers

Middle East respiratory syndrome coronavirus (MERS-CoV) is a lineage C betacoronavirus that since its emergence in 2012 has caused outbreaks in human populations with case-fatality rates of ∼36%. As in other coronaviruses, the spike (S) glycoprotein of MERS-CoV mediates receptor recognition and membrane fusion and is the primary target of the humoral immune response during infection. Here we use structure-based design to develop a generalizable strategy for retaining coronavirus S proteins in the antigenically optimal prefusion conformation and demonstrate that our engineered immunogen is able to elicit high neutralizing antibody titers against MERS-CoV. We also determined high-resolution structures of the trimeric MERS-CoV S ectodomain in complex with G4, a stem-directed neutralizing antibody. The structures reveal that G4 recognizes a glycosylated loop that is variable among coronaviruses and they define four conformational states of the trimer wherein each receptor-binding domain is either tightly packed at the membrane-distal apex or rotated into a receptor-accessible conformation. Our studies suggest a potential mechanism for fusion initiation through sequential receptor-binding events and provide a foundation for the structure-based design of coronavirus vaccines.

scholarly journals The Gammaherpesvirus Chemokine Binding Protein Binds to the N Terminus of CXCL8

2003 ◽  
Vol 77 (15) ◽  
pp. 8588-8592 ◽  
Author(s):  
Louise M. C. Webb ◽  
Ian Clark-Lewis ◽  
Antonio Alcami
Keyword(s):  
Receptor Binding ◽  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
Binding Protein ◽  
Sequence Similarity ◽  
Structural Requirements ◽  
Murine Gammaherpesvirus ◽  
N Terminus ◽  
Gammaherpesvirus 68 ◽  
Murine Gammaherpesvirus 68

ABSTRACT Viruses encode proteins that disrupt chemokine responses. The murine gammaherpesvirus 68 gene M3 encodes a chemokine binding protein (vCKBP-3) which has no sequence similarity to chemokine receptors but inhibits chemokine receptor binding and activity. We have used a panel of CXCL8 analogs to identify the structural requirements for CXCL8 to bind to vCKBP-3 in a scintillation proximity assay. Our data suggest that vCKBP-3 acts by mimicking the binding of chemokine receptors to CXCL8.

Structural requirements for gastric inhibitory polypeptide (GIP) receptor binding and stimulation of insulin release

Peptides ◽  
1986 ◽  
Vol 7 ◽  
pp. 75-78 ◽  
Author(s):  
Maura Maletti ◽  
Mats Carlquist ◽  
Bernard Portha ◽  
Micheline Kergoat ◽  
Viktor Mutt ◽  
...  
Keyword(s):  
Insulin Release ◽  
Receptor Binding ◽  
Gastric Inhibitory Polypeptide ◽  
Structural Requirements ◽  
Gip Receptor ◽  
Stimulation Of

Structural requirements of hyperalgesic nociceptin in receptor binding and activation

2006 ◽  
pp. 198-199
Author(s):  
T. Nose ◽  
R. Nakashima ◽  
R. Hatano ◽  
T. Sujaku ◽  
Y. Yamada ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Structural Requirements

scholarly journals Carcinoembryonic Antigen Family Receptor Recognition by Gonococcal Opa Proteins Requires Distinct Combinations of Hypervariable Opa Protein Domains

2002 ◽  
Vol 70 (4) ◽  
pp. 1715-1723 ◽  
Author(s):  
Martine P. Bos ◽  
David Kao ◽  
Daniel M. Hogan ◽  
Christopher C. R. Grant ◽  
Robert J. Belland
Keyword(s):  
Carcinoembryonic Antigen ◽  
Receptor Binding ◽  
Binding Activity ◽  
Host Cells ◽  
Sulfate Proteoglycan ◽  
Binding Properties ◽  
Receptor Binding Activity ◽  
Receptor Recognition ◽  
Strain Ms11 ◽  
Gonococcal Strain

ABSTRACT Neisserial Opa proteins function as a family of adhesins that bind heparan sulfate proteoglycan (HSPG) or carcinoembryonic antigen family (CEACAM) receptors on human host cells. In order to define the CEACAM binding domain on Opa proteins, we tested the binding properties of a series of gonococcal (strain MS11) recombinants producing mutant and chimeric Opa proteins with alterations in one or more of the four surface-exposed loops. Mutagenesis demonstrated that the semivariable domain, present in the first loop, was completely dispensable for CEACAM binding. In contrast, the two hypervariable (HV) regions present in the second and third loops were essential for binding; deletion of either domain resulted in loss of receptor recognition. Deletion of the fourth loop resulted in a severe decrease in Opa expression at the cell surface and could therefore not be tested for CEACAM binding. Chimeric Opa variants, containing combinations of HV regions derived from different CEACAM binding Opa proteins, lost most of their receptor binding activity. Some chimeric variants gained HSPG binding activity. Together, our results indicate that full recognition of CEACAM receptors by Opa proteins requires a highly coordinate interplay between both HV regions. Furthermore, shuffling of HV regions may result in novel HSPG receptor binding activity.

Glycan Structure Determinants for Cation-Independent Mannose 6-Phosphate Receptor Binding and Cellular Uptake of a Recombinant Protein

2013 ◽  
Vol 24 (12) ◽  
pp. 2025-2035 ◽  
Author(s):  
Qun Zhou ◽  
Luis Z. Avila ◽  
Paul A. Konowicz ◽  
John Harrahy ◽  
Patrick Finn ◽  
...  
Keyword(s):  
Recombinant Protein ◽  
Cellular Uptake ◽  
Receptor Binding ◽  
Glycan Structure ◽  
Mannose 6 Phosphate

scholarly journals Definition of a 14-Amino-Acid Peptide Essential for the Interaction between the Murine Leukemia Virus Amphotropic Envelope Glycoprotein and Its Receptor

1998 ◽  
Vol 72 (1) ◽  
pp. 428-435 ◽  
Author(s):  
Jean Luc Battini ◽  
Olivier Danos ◽  
Jean Michel Heard
Keyword(s):  
Amino Acid ◽  
Receptor Binding ◽  
Envelope Glycoprotein ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Target Cells ◽  
Structural Constraints ◽  
Binding Interaction ◽  
Receptor Recognition ◽  
Murine Leukemia

ABSTRACT Hydrophilic loops in the receptor binding domain of the amphotropic murine leukemia virus (MLV) envelope glycoprotein (SU) are predicted and may participate in SU-receptor interactions. We have replaced five segments of 6 to 15 amino acids located in each of these regions with an 11-amino-acid tag from the vesicular stomatitis virus glycoprotein (VSV-G). Substitution was compatible with envelope processing, transport, and incorporation into virions. However, three substitution mutants showed a temperature-dependent phenotype, suggesting structural unstability. Accessibility of the tagging epitope for a monoclonal anti-VSV-G antibody was greater in oligomeric than in monomeric SUs when insertion was done in VRA, a domain essential for receptor recognition. In contrast, accessibility was independent of structural constraints when insertion was done in VRB, a domain playing an accessory role in receptor binding. Interaction with the amphotropic receptor was investigated by interference assay and study of binding and infection of target cells with MLV particles coated with the substituted envelopes. Envelope-receptor interaction was abolished when substitution was performed in a potential loop-forming segment located at the N-terminal half of VRA. Although interaction was affected to variable extents, depending on the substituted segment, other mutants conserved the ability to interact with the amphotropic receptor. These experiments indicate the 14-amino-acid segment between positions 50 and 64 of SU as an essential determinant of amphotropic-receptor recognition. They also show that a foreign linear epitope can be tolerated in several locations of the amphotropic SU receptor binding site, and this result has implications for the design of targeted retroviral vectors.

scholarly journals Synthesis and receptor binding affinity of carboxylate analogues of the mannose 6-phosphate recognition marker

2006 ◽  
Vol 14 (10) ◽  
pp. 3575-3582 ◽  
Author(s):  
Audrey Jeanjean ◽  
Marcel Garcia ◽  
Alain Leydet ◽  
Jean-Louis Montero ◽  
Alain Morère
Keyword(s):  
Binding Affinity ◽  
Receptor Binding ◽  
Receptor Binding Affinity ◽  
Mannose 6 Phosphate

scholarly journals Cryo-EM structure of porcine delta coronavirus spike protein in the pre-fusion state

2017 ◽  
pp. JVI.01556-17 ◽  
Author(s):  
Jian Shang ◽  
Yuan Zheng ◽  
Yang Yang ◽  
Chang Liu ◽  
Qibin Geng ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Receptor Binding ◽  
Immune Evasion ◽  
Amino Acid Sequences ◽  
Spike Protein ◽  
Structural Elements ◽  
Compact Structure ◽  
Terminal Domain ◽  
Receptor Recognition ◽  
Spike Proteins

Coronavirus spike proteins from different genera are divergent, although they all mediate coronavirus entry into cells by binding to host receptors and fusing viral and cell membranes. Here we determined the cryo-EM structure of porcine delta coronavirus (PdCoV) spike protein at 3.3-angstrom resolution. The trimeric protein contains three receptor-binding S1 subunits that tightly pack into a crown-like structure and three membrane-fusion S2 subunits that form a stalk. Each S1 subunit contains two domains, N-terminal domain (S1-NTD) and C-terminal domain (S1-CTD). PdCoV S1-NTD has the same structural fold as alpha- and beta-coronavirus S1-NTDs as well as host galectins, and it recognizes sugar as its potential receptor. PdCoV S1-CTD has the same structural fold as alpha-coronavirus S1-CTDs, but its structure differs from that of beta-coronavirus S1-CTDs. PdCoV S1-CTD binds to an unidentified receptor on host cell surfaces. PdCoV S2 is locked in the pre-fusion conformation by structural restraint of S1 from a different monomeric subunit. PdCoV spike possesses several structural features that may facilitate immune evasion by the virus, such as its compact structure, concealed receptor-binding sites, and shielded critical epitopes. Overall, this study reveals that delta-coronavirus spikes are structurally and evolutionally more closely related to alpha-coronavirus spikes than to beta-coronavirus spikes; it also has implications for the receptor recognition, membrane fusion, and immune evasion by delta-coronaviruses as well as coronaviruses in general.SIGNIFICANCEIn this study we determined the cryo-EM structure of porcine delta coronavirus (PdCoV) spike protein at 3.3 angstrom. This is the first atomic structure of a spike protein from the delta coronavirus genus, which is divergent in amino acid sequences from the well-studied alpha- and beta-coronavirus spike proteins. In the current study, we described the overall structure of the PdCoV spike and the detailed structure of each of its structural elements. Moreover, we analyzed the functions of each of the structural elements. Based on the structures and functions of these structural elements, we discussed the evolution of PdCoV spike protein in relation to the spike proteins from other coronavirus genera. This study combines the structure, function, and evolution of coronavirus spike proteins, and provides many insights into the receptor recognition, membrane fusion, immune evasion, and evolution of PdCoV spike protein.

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