6OUS

Structure of fusion glycoprotein from human respiratory syncytial virus

PDB DOI: https://doi.org/10.2210/pdb6OUS/pdb

Classification: VIRAL PROTEIN/Immune system
Organism(s): Human respiratory syncytial virus A2, Human immunodeficiency virus 1, Homo sapiens
Expression System: Homo sapiens, Cricetulus griseus
Mutation(s): No

Deposited: 2019-05-05 Released: 2019-10-30
Deposition Author(s): Su, H.P.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 3.40 Å
R-Value Free: 0.275
R-Value Work: 0.245

Starting Models: experimental
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Ligand Structure Quality Assessment

This is version 3.2 of the entry. See complete history.

Literature

A potent broadly neutralizing human RSV antibody targets conserved site IV of the fusion glycoprotein.

Tang, A., Chen, Z., Cox, K.S., Su, H.P., Callahan, C., Fridman, A., Zhang, L., Patel, S.B., Cejas, P.J., Swoyer, R., Touch, S., Citron, M.P., Govindarajan, D., Luo, B., Eddins, M., Reid, J.C., Soisson, S.M., Galli, J., Wang, D., Wen, Z., Heidecker, G.J., Casimiro, D.R., DiStefano, D.J., Vora, K.A.

(2019) Nat Commun 10: 4153-4153

PubMed: 31515478 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1038/s41467-019-12137-1
Primary Citation of Related Structures:
6OUS

PubMed Abstract:
Respiratory syncytial virus (RSV) infection is the leading cause of hospitalization and infant mortality under six months of age worldwide; therefore, the prevention of RSV infection in all infants represents a significant unmet medical need. Here we report the isolation of a potent and broadly neutralizing RSV monoclonal antibody derived from a human memory B-cell. This antibody, RB1, is equipotent on RSV A and B subtypes, potently neutralizes a diverse panel of clinical isolates in vitro and demonstrates in vivo protection. It binds to a highly conserved epitope in antigenic site IV of the RSV fusion glycoprotein. RB1 is the parental antibody to MK-1654 which is currently in clinical development for the prevention of RSV infection in infants.

Organizational Affiliation

Department of Infectious Diseases and Vaccines Research, Merck & Co., Inc, West Point, PA, USA.

Macromolecule Content

Total Structure Weight: 623.85 kDa
Atom Count: 41,597
Modelled Residue Count: 5,451
Deposited Residue Count: 5,658
Unique protein chains: 4

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Fusion glycoprotein F2	A, C, E, G, I A, C, E, G, I, K	84	Human respiratory syncytial virus A2	Mutation(s): 0
UniProt
Find proteins for P03420 (Human respiratory syncytial virus A (strain A2)) Explore P03420 Go to UniProtKB: P03420
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P03420
Glycosylation
Glycosylation Sites: 1	Glycosylation Focus chain A Focus chain C Focus chain E Focus chain G Focus chain I Focus chain K
Sequence Annotations Expand
Reference Sequence

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Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
Fusion glycoprotein F1 fused with Fibritin trimerization domain	B, D, F, H, J B, D, F, H, J, L	414	Human respiratory syncytial virus A2, Human immunodeficiency virus 1 This entity is chimeric	Mutation(s): 0
UniProt
Find proteins for M1E1E4 (Human immunodeficiency virus type 1) Explore M1E1E4 Go to UniProtKB: M1E1E4
Find proteins for P03420 (Human respiratory syncytial virus A (strain A2)) Explore P03420 Go to UniProtKB: P03420
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Groups	M1E1E4P03420
Glycosylation
Glycosylation Sites: 1	Glycosylation Focus chain B Focus chain J Focus chain L
Sequence Annotations Expand
Reference Sequence

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(by identity cutoff) | 3D Structure

Entity ID: 3
Molecule	Chains	Sequence Length	Organism	Details	Image
RB1 Fab Heavy Chain	M, O, Q, S, U M, O, Q, S, U, W	231	Homo sapiens	Mutation(s): 0
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations Expand
Reference Sequence

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(by identity cutoff) | 3D Structure

Entity ID: 4
Molecule	Chains	Sequence Length	Organism	Details	Image
RB1 Fab Light chain	N, P, R, T, V N, P, R, T, V, X	214	Homo sapiens	Mutation(s): 0
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations Expand
Reference Sequence

Oligosaccharides

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Entity ID: 5
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose	AA [auth a], BA [auth b], CA [auth c], DA [auth d], Y, AA [auth a], BA [auth b], CA [auth c], DA [auth d], Y, Z	4		N-Glycosylation	Interactions Focus chain AA [auth a] Focus chain BA [auth b] Focus chain CA [auth c] Focus chain DA [auth d] Focus chain Y Focus chain Z Interactions & Density Focus chain AA [auth a] Focus chain BA [auth b] Focus chain CA [auth c] Focus chain DA [auth d] Focus chain Y Focus chain Z
Glycosylation Resources
GlyTouCan: G81315DD GlyCosmos: G81315DD GlyGen: G81315DD

Small Molecules

Ligands 1 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
NAG Query on NAG Download Ideal Coordinates CCD File SDF format, chain EA [auth B] SDF format, chain FA [auth F] SDF format, chain GA [auth J] SDF format, chain HA [auth L] MOL2 format, chain EA [auth B] MOL2 format, chain FA [auth F] MOL2 format, chain GA [auth J] MOL2 format, chain HA [auth L] mmCIF format, chain EA [auth B] mmCIF format, chain FA [auth F] mmCIF format, chain GA [auth J] mmCIF format, chain HA [auth L]	EA [auth B], FA [auth F], GA [auth J], HA [auth L]	2-acetamido-2-deoxy-beta-D-glucopyranose C₈ H₁₅ N O₆ OVRNDRQMDRJTHS-FMDGEEDCSA-N		Interactions Focus chain EA [auth B] Focus chain FA [auth F] Focus chain GA [auth J] Focus chain HA [auth L] Interactions & Density Focus chain EA [auth B] Focus chain FA [auth F] Focus chain GA [auth J] Focus chain HA [auth L]

Modified Residues 1 Unique
ID	Chains	Type	Formula	2D Diagram	Parent
PCA Query on PCA	A, C, E, G, I A, C, E, G, I, K	L-PEPTIDE LINKING	C₅ H₇ N O₃		GLN

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 3.40 Å
R-Value Free: 0.275
R-Value Work: 0.245
Space Group: P 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 118.153	α = 87.24
b = 126.595	β = 79.15
c = 148.165	γ = 86.29

Software Package:

Software Name	Purpose
PHENIX	refinement
XDS	data reduction
Aimless	data scaling
PHASER	phasing
PDB_EXTRACT	data extraction

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2019-10-30

Deposition Author(s):

Su, H.P.

Revision History (Full details and data files)

Version 1.0: 2019-10-30
Type: Initial release
Version 2.0: 2019-12-25
Changes: Database references, Polymer sequence
Version 3.0: 2020-07-29
Type: Remediation
Reason: Carbohydrate remediation
Changes: Advisory, Atomic model, Data collection, Derived calculations, Structure summary
Version 3.1: 2023-10-11
Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary
Version 3.2: 2024-10-23
Changes: Structure summary