Crystal structure and solution state of the C-terminal head region of the narmovirus receptor binding protein
ABSTRACT Increased viral surveillance has led to the isolation and identification of numerous uncharacterized paramyxoviruses, rapidly expanding our understanding of paramyxoviral diversity beyond the bounds of known genera. Despite this diversity, a key feature that unites paramyxoviruses is the pr...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-10-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mbio.01391-23 |
| _version_ | 1797619700590444544 |
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| author | Alice J. Stelfox Kasopefoluwa Y. Oguntuyo Ilona Rissanen Karl Harlos Robert Rambo Benhur Lee Thomas A. Bowden |
| author_facet | Alice J. Stelfox Kasopefoluwa Y. Oguntuyo Ilona Rissanen Karl Harlos Robert Rambo Benhur Lee Thomas A. Bowden |
| author_sort | Alice J. Stelfox |
| collection | DOAJ |
| description | ABSTRACT Increased viral surveillance has led to the isolation and identification of numerous uncharacterized paramyxoviruses, rapidly expanding our understanding of paramyxoviral diversity beyond the bounds of known genera. Despite this diversity, a key feature that unites paramyxoviruses is the presence of a receptor-binding protein (RBP), which facilitates host-cell attachment and plays a fundamental role in determining host range. Here, we study the RBP presented on the surface of rodent-borne paramyxoviruses Mossman and Nariva (MosV and NarV, respectively), viruses that constitute founding members of the recently defined Narmovirus genus within the Paramyxoviridae family. Crystallographic analysis of the C-terminal head region of the dimeric MosV and NarV RBPs demonstrates that while these glycoproteins retain the canonical six-bladed β-propeller fold found in other paramyxoviral RBPs, they lack the structural motifs associated with established paramyxovirus host-cell receptor entry pathways. Consistent with MosV-RBP and NarV-RBP undergoing a distinct entry pathway from other characterized paramyxoviruses, structure-based phylogenetic analysis demonstrates that these six-bladed β-propeller head domains form a singular structural class that is distinct from other paramyxoviral RBPs. Additionally, using an integrated crystallographic and small-angle X-ray scattering analysis, we confirm that MosV-RBP and NarV-RBP form homodimeric arrangements that are distinct from those adopted by other paramyxovirus RBPs. Altogether, this investigation provides a molecular-level blueprint of the narmovirus RBP that broadens our understanding of the structural space and functional diversity available to paramyxovirus RBPs. IMPORTANCE Genetically diverse paramyxoviruses are united in their presentation of a receptor-binding protein (RBP), which works in concert with the fusion protein to facilitate host-cell entry. The C-terminal head region of the paramyxoviral RBP, a primary determinant of host-cell tropism and inter-species transmission potential, forms structurally distinct classes dependent upon protein and glycan receptor specificity. Here, we reveal the architecture of the C-terminal head region of the RBPs from Nariva virus (NarV) and Mossman virus (MosV), two archetypal rodent-borne paramyxoviruses within the recently established genus Narmovirus, family Paramyxoviridae. Our analysis reveals that while narmoviruses retain the general architectural features associated with paramyxoviral RBPs, namely, a six-bladed β-propeller fold, they lack the structural motifs associated with known receptor-mediated host-cell entry pathways. This investigation indicates that the RBPs of narmoviruses exhibit pathobiological features that are distinct from those of other paramyxoviruses. |
| first_indexed | 2024-03-11T08:30:34Z |
| format | Article |
| id | doaj.art-92817af984f24736a7422fd40ac06895 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-03-11T08:30:34Z |
| publishDate | 2023-10-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-92817af984f24736a7422fd40ac068952023-11-16T21:48:01ZengAmerican Society for MicrobiologymBio2150-75112023-10-0114510.1128/mbio.01391-23Crystal structure and solution state of the C-terminal head region of the narmovirus receptor binding proteinAlice J. Stelfox0Kasopefoluwa Y. Oguntuyo1Ilona Rissanen2Karl Harlos3Robert Rambo4Benhur Lee5Thomas A. Bowden6Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford , Oxford, United KingdomIcahn School of Medicine at Mount Sinai , New York, New York, USADivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford , Oxford, United KingdomDivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford , Oxford, United KingdomDiamond Light Source Ltd, Harwell Science & Innovation Campus , Oxford, United KingdomIcahn School of Medicine at Mount Sinai , New York, New York, USADivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford , Oxford, United KingdomABSTRACT Increased viral surveillance has led to the isolation and identification of numerous uncharacterized paramyxoviruses, rapidly expanding our understanding of paramyxoviral diversity beyond the bounds of known genera. Despite this diversity, a key feature that unites paramyxoviruses is the presence of a receptor-binding protein (RBP), which facilitates host-cell attachment and plays a fundamental role in determining host range. Here, we study the RBP presented on the surface of rodent-borne paramyxoviruses Mossman and Nariva (MosV and NarV, respectively), viruses that constitute founding members of the recently defined Narmovirus genus within the Paramyxoviridae family. Crystallographic analysis of the C-terminal head region of the dimeric MosV and NarV RBPs demonstrates that while these glycoproteins retain the canonical six-bladed β-propeller fold found in other paramyxoviral RBPs, they lack the structural motifs associated with established paramyxovirus host-cell receptor entry pathways. Consistent with MosV-RBP and NarV-RBP undergoing a distinct entry pathway from other characterized paramyxoviruses, structure-based phylogenetic analysis demonstrates that these six-bladed β-propeller head domains form a singular structural class that is distinct from other paramyxoviral RBPs. Additionally, using an integrated crystallographic and small-angle X-ray scattering analysis, we confirm that MosV-RBP and NarV-RBP form homodimeric arrangements that are distinct from those adopted by other paramyxovirus RBPs. Altogether, this investigation provides a molecular-level blueprint of the narmovirus RBP that broadens our understanding of the structural space and functional diversity available to paramyxovirus RBPs. IMPORTANCE Genetically diverse paramyxoviruses are united in their presentation of a receptor-binding protein (RBP), which works in concert with the fusion protein to facilitate host-cell entry. The C-terminal head region of the paramyxoviral RBP, a primary determinant of host-cell tropism and inter-species transmission potential, forms structurally distinct classes dependent upon protein and glycan receptor specificity. Here, we reveal the architecture of the C-terminal head region of the RBPs from Nariva virus (NarV) and Mossman virus (MosV), two archetypal rodent-borne paramyxoviruses within the recently established genus Narmovirus, family Paramyxoviridae. Our analysis reveals that while narmoviruses retain the general architectural features associated with paramyxoviral RBPs, namely, a six-bladed β-propeller fold, they lack the structural motifs associated with known receptor-mediated host-cell entry pathways. This investigation indicates that the RBPs of narmoviruses exhibit pathobiological features that are distinct from those of other paramyxoviruses.https://journals.asm.org/doi/10.1128/mbio.01391-23paramyxovirusvirus-host interactionsstructureglycoproteinviral attachment |
| spellingShingle | Alice J. Stelfox Kasopefoluwa Y. Oguntuyo Ilona Rissanen Karl Harlos Robert Rambo Benhur Lee Thomas A. Bowden Crystal structure and solution state of the C-terminal head region of the narmovirus receptor binding protein mBio paramyxovirus virus-host interactions structure glycoprotein viral attachment |
| title | Crystal structure and solution state of the C-terminal head region of the narmovirus receptor binding protein |
| title_full | Crystal structure and solution state of the C-terminal head region of the narmovirus receptor binding protein |
| title_fullStr | Crystal structure and solution state of the C-terminal head region of the narmovirus receptor binding protein |
| title_full_unstemmed | Crystal structure and solution state of the C-terminal head region of the narmovirus receptor binding protein |
| title_short | Crystal structure and solution state of the C-terminal head region of the narmovirus receptor binding protein |
| title_sort | crystal structure and solution state of the c terminal head region of the narmovirus receptor binding protein |
| topic | paramyxovirus virus-host interactions structure glycoprotein viral attachment |
| url | https://journals.asm.org/doi/10.1128/mbio.01391-23 |
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