Reconstruction of 3D structures of MET antibodies from electron microscopy 2D class averages

Qi Chen, Michal Vieth, David E. Timm, Christine Humblet, Dina Schneidman-Duhovny, Ilan E. Chemmama, Andrej Sali, Wei Zeng, Jirong Lu, Ling Liu

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Dynamics of three MET antibody constructs (IgG1, IgG2, and IgG4) and the IgG4-MET antigen complex was investigated by creating their atomic models with an integrative experimental and computational approach. In particular, we used two-dimensional (2D) Electron Microscopy (EM) images, image class averaging, homology modeling, Rapidly exploring Random Tree (RRT) structure sampling, and fitting of models to images, to find the relative orientations of antibody domains that are consistent with the EM images. We revealed that the conformational preferences of the constructs depend on the extent of the hinge flexibility. We also quantified how the MET antigen impacts on the conformational dynamics of IgG4. These observations allow to create testable hypothesis to investigate MET biology. Our protocol may also help describe structural diversity of other antigen systems at approximately 5 Å precision, as quantified by Root-Mean-Square Deviation (RMSD) among goodscoring models.

Original languageAmerican English
Article numbere0175758
JournalPLoS ONE
Volume12
Issue number4
DOIs
StatePublished - Apr 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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