Evidence map›Paper›PMID 31221961›Full record

ArticleScientific reports2019

Single-Molecule 3D Images of "Hole-Hole" IgG1 Homodimers by Individual-Particle Electron Tomography.

Dongsheng Lei, Jianfang Liu, Hongbin Liu, Thomas E Cleveland, John P Marino, Ming Lei, Gang Ren

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.8field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Cold Denaturation of Proteins in the Absence of Solvent: Implications for Protein Storage.Angewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2022
    Article
  6. Article
  7. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 2 countries.

Dongsheng LeiThe Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.
Jianfang LiuThe Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.
Hongbin LiuProtein Analytical Chemistry, Genentech Inc., South San Francisco, CA, 94080, USA.
Thomas E ClevelandInstitute for Bioscience and Biotechnology Research, National Institute of Standards and Technology and the University of Maryland, Rockville, MD, 20850, USA.ORCID http://orcid.org/0000-0003-1992-8450
John P MarinoInstitute for Bioscience and Biotechnology Research, National Institute of Standards and Technology and the University of Maryland, Rockville, MD, 20850, USA.
Ming LeiProtein Analytical Chemistry, Genentech Inc., South San Francisco, CA, 94080, USA. lei.ming@gene.com.ORCID http://orcid.org/0000-0002-1247-1358
Gang RenThe Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA. gren@lbl.gov.
Lawrence Berkeley National Laboratory · USNational Institute of Standards and Technology · USGene Therapy Laboratory · FR

Funding

Structure-Function Relationship Studies of the Plasma Lipid Transfer Proteins CETP and PLTPR01HL115153 · NHLBI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI REN, GANG · 2012 to 2021
$3.9M
Lipoprotein Structure and Function by Individual Particle Electron TomographyR01GM104427 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI REN, GANG · 2013 to 2016
$1.3M
NHLBI NIH HHS R01 HL115153NIGMS NIH HHS R01 GM104427
6 · The paper itself

Abstract

The engineering of immunoglobulin-G molecules (IgGs) is of wide interest for improving therapeutics, for example by modulating the activity or multiplexing the specificity of IgGs to recognize more than one antigen. Optimization of engineered IgG requires knowledge of three-dimensional (3D) structure of synthetic IgG. However, due to flexible nature of the molecules, their structural characterization is challenging. Here, we use our reported individual-particle electron tomography (IPET) method with optimized negative-staining (OpNS) for direct 3D reconstruction of individual IgG hole-hole homodimer molecules. The hole-hole homodimer is an undesired variant generated during the production of a bispecific antibody using the knob-into-hole heterodimer technology. A total of 64 IPET 3D density maps at ~15 Å resolutions were reconstructed from 64 individual molecules, revealing 64 unique conformations. In addition to the known Y-shaped conformation, we also observed an unusual X-shaped conformation. The 3D structure of the X-shaped conformation contributes to our understanding of the structural details of the interaction between two heavy chains in the Fc domain. The IPET approach, as an orthogonal technique to characterize the 3D structure of therapeutic antibodies, provides insight into the 3D structural variety and dynamics of heterogeneous IgG molecules.

Indexed as

Antibodies, BispecificElectron Microscope TomographyImaging, Three-DimensionalImmunoglobulin GMolecular ImagingNegative StainingProtein ConformationProtein MultimerizationAntibodies, BispecificImmunoglobulin G

Identifiers

PMID31221961
PMCPMC6586654
OpenAlexW2951273155

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.