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A Model Interaction for Structural Biology and Health Research: Implications of the Antibody D25 bound to the RSV Pre‐Fusion Glycoprotein (LB100)
Author(s) -
Cheranov Maksim,
Eaton Muriel,
Hattemer Mark,
McClain Amy,
Rajendiran Pranav,
Rana Riya,
Saripalli Nithin,
Singh Jai,
Yang Louise,
Kessler Eric,
Tuel Kelley,
Whalen Joseph,
Graham Barney,
McLellan Jason
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb100
Subject(s) - furin , glycoprotein , lipid bilayer fusion , viral entry , heptad repeat , trimer , neutralizing antibody , virus , chemistry , antibody , virology , microbiology and biotechnology , biology , peptide sequence , biochemistry , immunology , viral replication , dimer , gene , organic chemistry , enzyme
Respiratory syncytial virus (RSV) is a paramyxovirus that infects all infants by age 3 and causes extensive morbidity, hospitalization, and global mortality in young infants. RSV F is a type I fusion glycoprotein essential for viral entry into cells, and exists as a trimer of heterodimers. Furin cleavage produces F1 and F2 subunits and exposes the hydrophobic fusion peptide which is buried at the base of the cavity formed by the prefusion trimer. An unknown triggering event causes a major conformational rearrangement producing a 10 Å heptad repeat (HR) with fusion peptide exposed on the distal end positioned to pierce the target cell membrane. The C‐terminus HR anchored in the viral membrane then swings around to approximate the N‐terminus HR resulting in an anti‐parallel 6‐helix bundle pulling the virus and cell membranes together to mediate fusion and allow viral entry. The Blue Valley CAPS SMART (Students Modeling a Research Topic) Team modeled RSV F in complex with the human antibody D25 using JMol and 3D printing technology. D25 binds antigenic site Ø locking the protein in its prefusion state. The stabilized prefusion trimer has been shown to elicit antibodies to antigenic site Ø with potent neutralizing activity. Thus, solving the atomic structure of the prefusion RSV F facilitated development of a candidate vaccine now being produced for evaluation in clinical trials. Grant Funding Source : Supported by grants from the NIH‐SEPA and NIH‐CTSA.