Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

Publication Detail

Title: Prediction of the binding interface between monoclonal antibody m102.4 and Nipah attachment glycoprotein using structure-guided alanine scanning and computational docking.

Authors: Tit-Oon, Phanthakarn; Tharakaraman, Kannan; Artpradit, Charlermchai; Godavarthi, Abhinav; Sungkeeree, Pareenart; Sasisekharan, Varun; Kerdwong, Jarunee; Miller, Nathaniel Loren; Mahajan, Bhuvna; Khongmanee, Amnart; Ruchirawat, Mathuros; Sasisekharan, Ram; Fuangthong, Mayuree

Published In Sci Rep, (2020 10 26)

Abstract: Nipah Virus (NiV) has been designated as a priority disease with an urgent need for therapeutic development by World Health Organization. The monoclonal antibody m102.4 binds to the immunodominant NiV receptor-binding glycoprotein (GP), and potently neutralizes NiV, indicating its potential as a therapeutic agent. Although the co-crystal structure of m102.3, an m102.4 derivative, in complex with the GP of the related Hendra Virus (HeV) has been solved, the structural interaction between m102.4 and NiV is uncharacterized. Herein, we used structure-guided alanine-scanning mutagenesis to map the functional epitope and paratope residues that govern the antigen-antibody interaction. Our results revealed that the binding of m102.4 is mediated predominantly by two residues in the HCDR3 region, which is unusually small for an antibody-antigen interaction. We performed computational docking to generate a structural model of m102.4-NiV interaction. Our model indicates that m102.4 targets the common hydrophobic central cavity and a hydrophilic rim on the GP, as observed for the m102.3-HeV co-crystal, albeit with Fv orientation differences. In summary, our study provides insight into the m102.4-NiV interaction, demonstrating that structure-guided alanine-scanning and computational modeling can serve as the starting point for additional antibody reengineering (e.g. affinity maturation) to generate potential therapeutic candidates.

PubMed ID: 33106487 Exiting the NIEHS site

MeSH Terms: Alanine/chemistry; Alanine/genetics*; Animals; Antibodies, Monoclonal/chemistry; Antibodies, Monoclonal/immunology; Antibodies, Monoclonal/metabolism*; Antibodies, Neutralizing/chemistry; Antibodies, Neutralizing/immunology; Antibodies, Neutralizing/metabolism; Antigen-Antibody Complex/chemistry; Antigen-Antibody Complex/immunology; Antigen-Antibody Complex/metabolism; Computer Simulation*; Epitopes/immunology; Glycoproteins/chemistry; Glycoproteins/genetics; Glycoproteins/metabolism*; Henipavirus Infections/immunology; Henipavirus Infections/metabolism; Henipavirus Infections/virology*; Humans; Mutagenesis, Site-Directed; Nipah Virus/immunology; Nipah Virus/isolation & purification; Nipah Virus/metabolism*; Protein Structural Elements/immunology; Viral Envelope Proteins/chemistry; Viral Envelope Proteins/genetics; Viral Envelope Proteins/metabolism*

Back
to Top