6B3D

Crystal structure of anti-HIV antibody PGT128 in complex with a bacterially derived synthetic mimetic of Man9.

PDB DOI: https://doi.org/10.2210/pdb6B3D/pdb

Classification: IMMUNE SYSTEM
Organism(s): Homo sapiens
Expression System: Homo sapiens
Mutation(s): No

Deposited: 2017-09-21 Released: 2017-12-06
Deposition Author(s): Murrell, S., Wilson, I.A.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.27 Å
R-Value Free: 0.198
R-Value Work: 0.163
R-Value Observed: 0.165

wwPDB Validation 3D Report Full Report

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

Literature

Bacterially derived synthetic mimetics of mammalian oligomannose prime antibody responses that neutralize HIV infectivity.

Pantophlet, R., Trattnig, N., Murrell, S., Lu, N., Chau, D., Rempel, C., Wilson, I.A., Kosma, P.

(2017) Nat Commun 8: 1601-1601

PubMed: 29150603 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1038/s41467-017-01640-y
Primary Citation of Related Structures:
6B3D

PubMed Abstract:
Oligomannose-type glycans are among the major targets on the gp120 component of the HIV envelope protein (Env) for broadly neutralizing antibodies (bnAbs). However, attempts to elicit oligomannose-specific nAbs by immunizing with natural or synthetic oligomannose have so far not been successful, possibly due to B cell tolerance checkpoints. Here we design and synthesize oligomannose mimetics, based on the unique chemical structure of a recently identified bacterial lipooligosaccharide, to appear foreign to the immune system. One of these mimetics is bound avidly by members of a family of oligomannose-specific bnAbs and their putative common germline precursor when presented as a glycoconjugate. The crystal structure of one of the mimetics bound to a member of this bnAb family confirms the antigenic resemblance. Lastly, immunization of human-antibody transgenic animals with a lead mimetic evokes nAbs with specificities approaching those of existing bnAbs. These results provide evidence for utilizing antigenic mimicry to elicit oligomannose-specific bnAbs to HIV-1.

Organizational Affiliation

Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada, V5A1S6. rpantophlet@sfu.ca.

Macromolecule Content

Total Structure Weight: 50.01 kDa
Atom Count: 3,625
Modelled Residue Count: 442
Deposited Residue Count: 450
Unique protein chains: 2

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
PGT128 Fab light chain	A [auth L]	211	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: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
PGT128 Fab heavy chain	B [auth H]	239	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: 3
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose	C [auth A]	7		N/A	Interactions Focus chain C [auth A] Interactions & Density Focus chain C [auth A]
Glycosylation Resources
GlyTouCan: G28309CZ GlyCosmos: G28309CZ

Small Molecules

Ligands 4 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
EPE Query on EPE Download Ideal Coordinates CCD File SDF format, chain L [auth H] MOL2 format, chain L [auth H]	L [auth H]	4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID C₈ H₁₈ N₂ O₄ S JKMHFZQWWAIEOD-UHFFFAOYSA-N		Interactions Focus chain L [auth H] Interactions & Density Focus chain L [auth H]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain D [auth L] SDF format, chain E [auth L] SDF format, chain F [auth L] MOL2 format, chain D [auth L] MOL2 format, chain E [auth L] MOL2 format, chain F [auth L]	D [auth L], E [auth L], F [auth L]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain D [auth L] Focus chain E [auth L] Focus chain F [auth L] Interactions & Density Focus chain D [auth L] Focus chain E [auth L] Focus chain F [auth L]
EDO Query on EDO Download Ideal Coordinates CCD File SDF format, chain G [auth L] SDF format, chain H [auth L] SDF format, chain I [auth L] SDF format, chain J [auth L] SDF format, chain M [auth H] SDF format, chain N [auth H] MOL2 format, chain G [auth L] MOL2 format, chain H [auth L] MOL2 format, chain I [auth L] MOL2 format, chain J [auth L] MOL2 format, chain M [auth H] MOL2 format, chain N [auth H]	G [auth L] H [auth L] I [auth L] J [auth L] M [auth H] G [auth L], H [auth L], I [auth L], J [auth L], M [auth H], N [auth H]	1,2-ETHANEDIOL C₂ H₆ O₂ LYCAIKOWRPUZTN-UHFFFAOYSA-N		Interactions Focus chain G [auth L] Focus chain H [auth L] Focus chain I [auth L] Focus chain J [auth L] Focus chain M [auth H] Focus chain N [auth H] Interactions & Density Focus chain G [auth L] Focus chain H [auth L] Focus chain I [auth L] Focus chain J [auth L] Focus chain M [auth H] Focus chain N [auth H]
IPA Query on IPA Download Ideal Coordinates CCD File SDF format, chain K [auth L] SDF format, chain O [auth H] SDF format, chain P [auth H] MOL2 format, chain K [auth L] MOL2 format, chain O [auth H] MOL2 format, chain P [auth H]	K [auth L], O [auth H], P [auth H]	ISOPROPYL ALCOHOL C₃ H₈ O KFZMGEQAYNKOFK-UHFFFAOYSA-N		Interactions Focus chain K [auth L] Focus chain O [auth H] Focus chain P [auth H] Interactions & Density Focus chain K [auth L] Focus chain O [auth H] Focus chain P [auth H]

Modified Residues 1 Unique
ID	Chains	Type	Formula	2D Diagram	Parent
PCA Query on PCA	B [auth H]	L-PEPTIDE LINKING	C₅ H₇ N O₃		GLN

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.27 Å
R-Value Free: 0.198
R-Value Work: 0.163
R-Value Observed: 0.165
Space Group: C 2 2 2₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 72.137	α = 90
b = 105.204	β = 90
c = 145.306	γ = 90

Software Package:

Software Name	Purpose
PHENIX	refinement
HKL-2000	data reduction
HKL-2000	data scaling
PHASER	phasing

Structure Validation

View Full Validation Report

Entry History

Deposition Data

Released Date: 2017-12-06

Deposition Author(s):

Murrell, S.

Wilson, I.A.

Revision History (Full details and data files)

Version 1.0: 2017-12-06
Type: Initial release
Version 2.0: 2020-07-29
Type: Remediation
Reason: Carbohydrate remediation
Changes: Atomic model, Data collection, Derived calculations, Polymer sequence, Structure summary
Version 2.1: 2023-10-04
Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary