6FYS

Structure of single domain antibody SD83

PDB DOI: https://doi.org/10.2210/pdb6FYS/pdb

Classification: VIRAL PROTEIN
Organism(s): Lama glama
Expression System: Homo sapiens
Mutation(s): No

Deposited: 2018-03-12 Released: 2018-11-07
Deposition Author(s): Laursen, N.S., Wilson, I.A.
Funding Organization(s): National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.00 Å
R-Value Free: 0.231
R-Value Work: 0.201
R-Value Observed: 0.202

wwPDB Validation 3D Report Full Report

This is version 1.3 of the entry. See complete history.

Literature

Universal protection against influenza infection by a multidomain antibody to influenza hemagglutinin.

Laursen, N.S., Friesen, R.H.E., Zhu, X., Jongeneelen, M., Blokland, S., Vermond, J., van Eijgen, A., Tang, C., van Diepen, H., Obmolova, G., van der Neut Kolfschoten, M., Zuijdgeest, D., Straetemans, R., Hoffman, R.M.B., Nieusma, T., Pallesen, J., Turner, H.L., Bernard, S.M., Ward, A.B., Luo, J., Poon, L.L.M., Tretiakova, A.P., Wilson, J.M., Limberis, M.P., Vogels, R., Brandenburg, B., Kolkman, J.A., Wilson, I.A.

(2018) Science 362: 598-602

PubMed: 30385580 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1126/science.aaq0620
Primary Citation of Related Structures:
6CK8, 6CNV, 6CNW, 6FYS, 6FYT, 6FYU, 6FYW

PubMed Abstract:
Broadly neutralizing antibodies against highly variable pathogens have stimulated the design of vaccines and therapeutics. We report the use of diverse camelid single-domain antibodies to influenza virus hemagglutinin to generate multidomain antibodies with impressive breadth and potency. Multidomain antibody MD3606 protects mice against influenza A and B infection when administered intravenously or expressed locally from a recombinant adeno-associated virus vector. Crystal and single-particle electron microscopy structures of these antibodies with hemagglutinins from influenza A and B viruses reveal binding to highly conserved epitopes. Collectively, our findings demonstrate that multidomain antibodies targeting multiple epitopes exhibit enhanced virus cross-reactivity and potency. In combination with adeno-associated virus-mediated gene delivery, they may provide an effective strategy to prevent infection with influenza virus and other highly variable pathogens.

Organizational Affiliation

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

Macromolecule Content

Total Structure Weight: 111.01 kDa
Atom Count: 7,850
Modelled Residue Count: 1,009
Deposited Residue Count: 1,032
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Single domain antibody SD83	A [auth C] B [auth A] C [auth B] D E A [auth C], B [auth A], C [auth B], D, E, F, G, H	129	Lama glama	Mutation(s): 0
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 1 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
EDO Query on EDO Download Ideal Coordinates CCD File SDF format, chain I [auth D] SDF format, chain J [auth F] SDF format, chain K [auth H] SDF format, chain L [auth H] SDF format, chain M [auth H] MOL2 format, chain I [auth D] MOL2 format, chain J [auth F] MOL2 format, chain K [auth H] MOL2 format, chain L [auth H] MOL2 format, chain M [auth H] mmCIF format, chain I [auth D] mmCIF format, chain J [auth F] mmCIF format, chain K [auth H] mmCIF format, chain L [auth H] mmCIF format, chain M [auth H]	I [auth D], J [auth F], K [auth H], L [auth H], M [auth H]	1,2-ETHANEDIOL C₂ H₆ O₂ LYCAIKOWRPUZTN-UHFFFAOYSA-N		Interactions Focus chain I [auth D] Focus chain J [auth F] Focus chain K [auth H] Focus chain L [auth H] Focus chain M [auth H] Interactions & Density Focus chain I [auth D] Focus chain J [auth F] Focus chain K [auth H] Focus chain L [auth H] Focus chain M [auth H]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.00 Å
R-Value Free: 0.231
R-Value Work: 0.201
R-Value Observed: 0.202
Space Group: P 1 2₁ 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 63.96	α = 90
b = 85.7	β = 93.96
c = 103.78	γ = 90

Software Package:

Software Name	Purpose
PHENIX	refinement
XDS	data reduction
XSCALE	data scaling
PHASER	phasing

Structure Validation

View Full Validation Report

Entry History & Funding Information

Deposition Data

Released Date: 2018-11-07

Deposition Author(s):

Laursen, N.S.

Wilson, I.A.

Funding Organization	Location	Grant Number
National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)	United States	R56 AI117675
National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)	United States	R56 AI127371

Revision History (Full details and data files)

Version 1.0: 2018-11-07
Type: Initial release
Version 1.1: 2018-11-14
Changes: Data collection, Database references, Derived calculations
Version 1.2: 2022-03-30
Changes: Author supporting evidence, Database references
Version 1.3: 2024-11-13
Changes: Data collection, Structure summary