6NHQ

Crystal structure of the A/Hong Kong/1/1968 (H3N2) influenza virus hemagglutinin HA2 I45M mutant

PDB DOI: https://doi.org/10.2210/pdb6NHQ/pdb

Classification: VIRAL PROTEIN
Organism(s): Influenza A virus (A/Hong Kong/1/1968(H3N2))
Expression System: Trichoplusia ni
Mutation(s): Yes

Deposited: 2018-12-23 Released: 2020-04-15
Deposition Author(s): Wu, N.C., Wilson, I.A.
Funding Organization(s): National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.50 Å
R-Value Free: 0.219
R-Value Work: 0.190
R-Value Observed: 0.192

wwPDB Validation 3D Report Full Report

Currently 6NHQ does not have a validation slider image.

This is version 2.1 of the entry. See complete history.

Literature

Different genetic barriers for resistance to HA stem antibodies in influenza H3 and H1 viruses.

Wu, N.C., Thompson, A.J., Lee, J.M., Su, W., Arlian, B.M., Xie, J., Lerner, R.A., Yen, H.L., Bloom, J.D., Wilson, I.A.

(2020) Science 368: 1335-1340

PubMed: 32554590 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1126/science.aaz5143
Primary Citation of Related Structures:
6NHP, 6NHQ, 6NHR

PubMed Abstract:
The discovery and characterization of broadly neutralizing human antibodies (bnAbs) to the highly conserved stem region of influenza hemagglutinin (HA) have contributed to considerations of a universal influenza vaccine. However, the potential for resistance to stem bnAbs also needs to be more thoroughly evaluated. Using deep mutational scanning, with a focus on epitope residues, we found that the genetic barrier to resistance to stem bnAbs is low for the H3 subtype but substantially higher for the H1 subtype owing to structural differences in the HA stem. Several strong resistance mutations in H3 can be observed in naturally circulating strains and do not reduce in vitro viral fitness and in vivo pathogenicity. This study highlights a potential challenge for development of a truly universal influenza vaccine.

Organizational Affiliation

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Macromolecule Content

Total Structure Weight: 171.45 kDa
Atom Count: 12,165
Modelled Residue Count: 1,469
Deposited Residue Count: 1,491
Unique protein chains: 2

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Hemagglutinin HA1 chain	A, C, E	321	Influenza A virus (A/Hong Kong/1/1968(H3N2))	Mutation(s): 0 Gene Names: HA
UniProt
Find proteins for Q91MA7 (Influenza A virus (strain A/Hong Kong/1/1968 H3N2)) Explore Q91MA7 Go to UniProtKB: Q91MA7
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q91MA7
Sequence Annotations Expand
Reference Sequence

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
Hemagglutinin HA2 chain	B, D, F	176	Influenza A virus (A/Hong Kong/1/1968(H3N2))	Mutation(s): 1 Gene Names: HA
UniProt
Find proteins for Q91MA7 (Influenza A virus (strain A/Hong Kong/1/1968 H3N2)) Explore Q91MA7 Go to UniProtKB: Q91MA7
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q91MA7
Sequence Annotations Expand
Reference Sequence

Oligosaccharides

Help

Entity ID: 3
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose	G, H	3		N-Glycosylation	Interactions Focus chain G Focus chain H Interactions & Density Focus chain G Focus chain H
Glycosylation Resources
GlyTouCan: G15407YE GlyCosmos: G15407YE GlyGen: G15407YE

Entity ID: 4
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose	I, K	2		N-Glycosylation	Interactions Focus chain I Focus chain K Interactions & Density Focus chain I Focus chain K
Glycosylation Resources
GlyTouCan: G42666HT GlyCosmos: G42666HT GlyGen: G42666HT

Entity ID: 5
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose	J	4		N-Glycosylation	Interactions Focus chain J Interactions & Density Focus chain J
Glycosylation Resources
GlyTouCan: G22573RC GlyCosmos: G22573RC GlyGen: G22573RC

Entity ID: 6
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	L	4		N-Glycosylation	Interactions Focus chain L Interactions & Density Focus chain L
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 M [auth A] SDF format, chain N [auth C] SDF format, chain O [auth C] SDF format, chain P [auth D] SDF format, chain Q [auth E] SDF format, chain R [auth E] MOL2 format, chain M [auth A] MOL2 format, chain N [auth C] MOL2 format, chain O [auth C] MOL2 format, chain P [auth D] MOL2 format, chain Q [auth E] MOL2 format, chain R [auth E]	M [auth A] N [auth C] O [auth C] P [auth D] Q [auth E] M [auth A], N [auth C], O [auth C], P [auth D], Q [auth E], R [auth E]	2-acetamido-2-deoxy-beta-D-glucopyranose C₈ H₁₅ N O₆ OVRNDRQMDRJTHS-FMDGEEDCSA-N		Interactions Focus chain M [auth A] Focus chain N [auth C] Focus chain O [auth C] Focus chain P [auth D] Focus chain Q [auth E] Focus chain R [auth E] Interactions & Density Focus chain M [auth A] Focus chain N [auth C] Focus chain O [auth C] Focus chain P [auth D] Focus chain Q [auth E] Focus chain R [auth E]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.50 Å
R-Value Free: 0.219
R-Value Work: 0.190
R-Value Observed: 0.192
Space Group: C 1 2 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 208.856	α = 90
b = 131.006	β = 98.4
c = 72.576	γ = 90

Software Package:

Software Name	Purpose
HKL-2000	data scaling
PHASER	phasing
REFMAC	refinement

Structure Validation

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Currently 6NHQ does not have a validation slider image.

Entry History & Funding Information

Deposition Data

Released Date: 2020-04-15

Deposition Author(s):

Wu, N.C.

Wilson, I.A.

Funding Organization	Location	Grant Number
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)	United States	R56 AI127371

Revision History (Full details and data files)

Version 1.0: 2020-04-15
Type: Initial release
Version 1.1: 2020-06-17
Changes: Database references
Version 1.2: 2020-07-01
Changes: Database references
Version 2.0: 2020-07-29
Type: Remediation
Reason: Carbohydrate remediation
Changes: Atomic model, Data collection, Derived calculations, Structure summary
Version 2.1: 2023-10-11
Changes: Data collection, Database references, Refinement description, Structure summary