5DFW

CRYSTAL STRUCTURE OF HUMAN CD81 LARGE EXTRACELLULAR LOOP IN COMPLEX WITH SINGLE CHAIN FV FRAGMENT K13

Summary for 5DFW

• Entry DOI: 10.2210/pdb5dfw/pdb
• Related: 5DFV
• Descriptor: CD81 antigen, SINGLE CHAIN FV FRAGMENT (3 entities in total)
• Functional Keywords: helical bundle, antibody-antigen complex, cell adhesion
• Biological source: Homo sapiens (Human); More
• Cellular location: Membrane; Multi-pass membrane protein: P60033
• Total number of polymer chains: 2
• Total formula weight: 36658.51

Authors

Harris, S.F.,Villasenor, A.,Kuglstatter, A. (deposition date: 2015-08-27, release date: 2015-12-16, Last modification date: 2024-10-23)

Primary citation

Bujotzek, A.,Lipsmeier, F.,Harris, S.F.,Benz, J.,Kuglstatter, A.,Georges, G.
VH-VL orientation prediction for antibody humanization candidate selection: A case study.
Mabs, 8:288-305, 2016

PubMed Abstract: Antibody humanization describes the procedure of grafting a non-human antibody's complementarity-determining regions, i.e., the variable loop regions that mediate specific interactions with the antigen, onto a β-sheet framework that is representative of the human variable region germline repertoire, thus reducing the number of potentially antigenic epitopes that might trigger an anti-antibody response. The selection criterion for the so-called acceptor frameworks (one for the heavy and one for the light chain variable region) is traditionally based on sequence similarity. Here, we propose a novel approach that selects acceptor frameworks such that the relative orientation of the 2 variable domains in 3D space, and thereby the geometry of the antigen-binding site, is conserved throughout the process of humanization. The methodology relies on a machine learning-based predictor of antibody variable domain orientation that has recently been shown to improve the quality of antibody homology models. Using data from 3 humanization campaigns, we demonstrate that preselecting humanization variants based on the predicted difference in variable domain orientation with regard to the original antibody leads to subsets of variants with a significant improvement in binding affinity.

PubMed: 26637054
DOI: 10.1080/19420862.2015.1117720

Experimental method

X-RAY DIFFRACTION (2.33 Å)