TY - JOUR
T1 - Computational-guided determination of the functional role of 447-52D long CDRH3
AU - Kamau, Edwin
AU - Bonneau, Richard
AU - Kong, Xiang Peng
N1 - Funding Information:
We thank Dr Paramjit Arora and his lab members for helping with the fluorescence polarization assay, Dr Xueling Wu at ADARC for providing us with gp120 of YU2 strain, and Christina Luo for carefully reading the manuscript. This study was supported in part by NIH grant AI100151.
Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press. All rights reserved.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 447-52D (447) is a human monoclonal antibody that recognizes a conserved epitope in the crown region of the third variable loop (V3) of HIV-1 gp120, and like many anti-HIV-1 antibodies with broad neutralization capabilities, it has a long heavy-chain complementarity determining region (CDRH3). Here, we use a combination of computational mutagenesis and modeling in tandem with fluorescence polarization assays to interrogate the molecular basis of 447 CDRH3 length and the individual contribution of selected CDRH3 residues to affinity. We observe that 447 CDRH3 length provides a large binding surface area and the best enthalpic contributions derived from hydrophobic packing, main-chain hydrogen bonds, electrostatic and van der Waals interactions. We also found out that CDRH3 residue Try100I is critical to 447 binding affinity.
AB - 447-52D (447) is a human monoclonal antibody that recognizes a conserved epitope in the crown region of the third variable loop (V3) of HIV-1 gp120, and like many anti-HIV-1 antibodies with broad neutralization capabilities, it has a long heavy-chain complementarity determining region (CDRH3). Here, we use a combination of computational mutagenesis and modeling in tandem with fluorescence polarization assays to interrogate the molecular basis of 447 CDRH3 length and the individual contribution of selected CDRH3 residues to affinity. We observe that 447 CDRH3 length provides a large binding surface area and the best enthalpic contributions derived from hydrophobic packing, main-chain hydrogen bonds, electrostatic and van der Waals interactions. We also found out that CDRH3 residue Try100I is critical to 447 binding affinity.
KW - antibody
KW - antigen-binding site
KW - complementarity determining region
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U2 - 10.1093/protein/gzz007
DO - 10.1093/protein/gzz007
M3 - Article
C2 - 31038677
AN - SCOPUS:85070182951
SN - 1741-0126
VL - 31
SP - 479
EP - 487
JO - Protein Engineering, Design and Selection
JF - Protein Engineering, Design and Selection
IS - 12
ER -