Structural Transition and Antibody Binding of EBOV GP and ZIKV E Proteins from Pre-Fusion to Fusion-Initiation State

• Main Authors: Anna Lappala, Wataru Nishima, Jacob Miner, Paul Fenimore, Will Fischer, Peter Hraber, Ming Zhang, Benjamin McMahon, Chang-Shung Tung
• Format: Article
• Language: English
• Published: MDPI AG 2018-05-01
• Series: Biomolecules
• Subjects: EBOV GP; ZIKV E; pre-fusion-to-fusion transition; antibody binding
• Online Access: http://www.mdpi.com/2218-273X/8/2/25

Membrane fusion proteins are responsible for viral entry into host cells—a crucial first step in viral infection. These proteins undergo large conformational changes from pre-fusion to fusion-initiation structures, and, despite differences in viral genomes and disease etiology, many fusion proteins are arranged as trimers. Structural information for both pre-fusion and fusion-initiation states is critical for understanding virus neutralization by the host immune system. In the case of Ebola virus glycoprotein (EBOV GP) and Zika virus envelope protein (ZIKV E), pre-fusion state structures have been identified experimentally, but only partial structures of fusion-initiation states have been described. While the fusion-initiation structure is in an energetically unfavorable state that is difficult to solve experimentally, the existing structural information combined with computational approaches enabled the modeling of fusion-initiation state structures of both proteins. These structural models provide an improved understanding of four different neutralizing antibodies in the prevention of viral host entry.