4JDV

Crystal structure of germ-line precursor of NIH45-46 Fab

PDB DOI: https://doi.org/10.2210/pdb4JDV/pdb

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

Deposited: 2013-02-25 Released: 2013-03-20
Deposition Author(s): Diskin, R., Scharf, L., Bjorkman, P.J.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.65 Å
R-Value Free: 0.203
R-Value Work: 0.174
R-Value Observed: 0.174

wwPDB Validation 3D Report Full Report

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

Literature

Structural basis for HIV-1 gp120 recognition by a germ-line version of a broadly neutralizing antibody.

Scharf, L., West, A.P., Gao, H., Lee, T., Scheid, J.F., Nussenzweig, M.C., Bjorkman, P.J., Diskin, R.

(2013) Proc Natl Acad Sci U S A 110: 6049-6054

PubMed: 23524883 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1073/pnas.1303682110
Primary Citation of Related Structures:
4JDT, 4JDV

PubMed Abstract:
Efforts to design an effective antibody-based vaccine against HIV-1 would benefit from understanding how germ-line B-cell receptors (BCRs) recognize the HIV-1 gp120/gp41 envelope spike. Potent VRC01-like (PVL) HIV-1 antibodies derived from the VH1-2*02 germ-line allele target the conserved CD4 binding site on gp120. A bottleneck for design of immunogens capable of eliciting PVL antibodies is that VH1-2*02 germ-line BCR interactions with gp120 are uncharacterized. Here, we report the structure of a VH1-2*02 germ-line antibody alone and a germ-line heavy-chain/mature light-chain chimeric antibody complexed with HIV-1 gp120. VH1-2*02 residues make extensive contacts with the gp120 outer domain, including all PVL signature and CD4 mimicry interactions, but not critical CDRH3 contacts with the gp120 inner domain and bridging sheet that are responsible for the improved potency of NIH45-46 over closely related clonal variants, such as VRC01. Our results provide insight into initial recognition of HIV-1 by VH1-2*02 germ-line BCRs and may facilitate the design of immunogens tailored to engage and stimulate broad and potent CD4 binding site antibodies.

Organizational Affiliation

Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.

Macromolecule Content

Total Structure Weight: 97.7 kDa
Atom Count: 7,597
Modelled Residue Count: 859
Deposited Residue Count: 884
Unique protein chains: 2

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Fab heavy chain	A, C [auth H]	232	Homo sapiens	Mutation(s): 0
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations Expand
Reference Sequence

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
Fab light chain	B, D [auth L]	210	Homo sapiens	Mutation(s): 0
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 4 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
1PE Query on 1PE Download Ideal Coordinates CCD File SDF format, chain N [auth L] SDF format, chain L [auth H] MOL2 format, chain N [auth L] MOL2 format, chain L [auth H]	L [auth H], N [auth L]	PENTAETHYLENE GLYCOL C₁₀ H₂₂ O₆ JLFNLZLINWHATN-UHFFFAOYSA-N		Interactions Focus chain L [auth H] Focus chain N [auth L] Interactions & Density Focus chain L [auth H] Focus chain N [auth L]
144 Query on 144 Download Ideal Coordinates CCD File SDF format, chain H [auth A] SDF format, chain K [auth H] MOL2 format, chain H [auth A] MOL2 format, chain K [auth H]	H [auth A], K [auth H]	TRIS-HYDROXYMETHYL-METHYL-AMMONIUM C₄ H₁₂ N O₃ DRDCQJADRSJFFD-UHFFFAOYSA-N		Interactions Focus chain H [auth A] Focus chain K [auth H] Interactions & Density Focus chain H [auth A] Focus chain K [auth H]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain I [auth B] SDF format, chain M [auth L] SDF format, chain E [auth A] MOL2 format, chain F [auth A] MOL2 format, chain I [auth B] MOL2 format, chain M [auth L] MOL2 format, chain E [auth A]	E [auth A], F [auth A], I [auth B], M [auth L]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain E [auth A] Focus chain F [auth A] Focus chain I [auth B] Focus chain M [auth L] Interactions & Density Focus chain E [auth A] Focus chain F [auth A] Focus chain I [auth B] Focus chain M [auth L]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain J [auth B] SDF format, chain G [auth A] MOL2 format, chain J [auth B] MOL2 format, chain G [auth A]	G [auth A], J [auth B]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain G [auth A] Focus chain J [auth B] Interactions & Density Focus chain G [auth A] Focus chain J [auth B]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.65 Å
R-Value Free: 0.203
R-Value Work: 0.174
R-Value Observed: 0.174
Space Group: P 2₁ 2₁ 2₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 55.96	α = 90
b = 70.14	β = 90
c = 225.11	γ = 90

Software Package:

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

Structure Validation

View Full Validation Report

Entry History

Deposition Data

Released Date: 2013-03-20

Deposition Author(s):

Diskin, R.

Scharf, L.

Bjorkman, P.J.

Revision History (Full details and data files)

Version 1.0: 2013-03-20
Type: Initial release
Version 1.1: 2013-05-08
Changes: Database references
Version 1.2: 2021-06-02
Changes: Derived calculations, Source and taxonomy
Version 1.3: 2023-09-20
Changes: Data collection, Database references, Refinement description