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J Mol Recognit. 2018 May;31(5):e2693. doi: 10.1002/jmr.2693. Epub 2017 Dec 8.

Local and global anatomy of antibody-protein antigen recognition.

Author information

1
Basic Science Program, Leidos Biomedical Research, Inc, Cancer and Inflammation Program, National Cancer Institute, Frederick, MD, USA.
2
School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
3
Sackler Institute of Molecular Medicine, Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Abstract

Deciphering antibody-protein antigen recognition is of fundamental and practical significance. We constructed an antibody structural dataset, partitioned it into human and murine subgroups, and compared it with nonantibody protein-protein complexes. We investigated the physicochemical properties of regions on and away from the antibody-antigen interfaces, including net charge, overall antibody charge distributions, and their potential role in antigen interaction. We observed that amino acid preference in antibody-protein antigen recognition is entropy driven, with residues having low side-chain entropy appearing to compensate for the high backbone entropy in interaction with protein antigens. Antibodies prefer charged and polar antigen residues and bridging water molecules. They also prefer positive net charge, presumably to promote interaction with negatively charged protein antigens, which are common in proteomes. Antibody-antigen interfaces have large percentages of Tyr, Ser, and Asp, but little Lys. Electrostatic and hydrophobic interactions in the Ag binding sites might be coupled with Fab domains through organized charge and residue distributions away from the binding interfaces. Here we describe some features of antibody-antigen interfaces and of Fab domains as compared with nonantibody protein-protein interactions. The distributions of interface residues in human and murine antibodies do not differ significantly. Overall, our results provide not only a local but also a global anatomy of antibody structures.

KEYWORDS:

allosteric regulation; antibody-antigen recognition; binding epitopes; mAb drugs; protein-protein interaction

PMID:
29218757
PMCID:
PMC5903993
DOI:
10.1002/jmr.2693
[Indexed for MEDLINE]
Free PMC Article

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