Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion

Cell
Alexandra C WallsDavid Veesler

Abstract

Recent outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome, along with the threat of a future coronavirus-mediated pandemic, underscore the importance of finding ways to combat these viruses. The trimeric spike transmembrane glycoprotein S mediates entry into host cells and is the major target of neutralizing antibodies. To understand the humoral immune response elicited upon natural infections with coronaviruses, we structurally characterized the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors. Although the two antibodies studied blocked attachment to the host cell receptor, only the anti-SARS-CoV S antibody triggered fusogenic conformational changes via receptor functional mimicry. These results provide a structural framework for understanding coronavirus neutralization by human antibodies and shed light on activation of coronavirus membrane fusion, which takes place through a receptor-driven ratcheting mechanism.

Citations

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Datasets Mentioned

BETA
JX869059.2
KC164505.2
PDX010494

Methods Mentioned

BETA
glycosylation
glycosylations
size-exclusion chromatography
electron microscopy
biosensors
transfection
gel filtration
biolayer interferometry

Software Mentioned

UCSF Chimera
privateer
Appion
Phenix
Aimless
DogPicker
Phaser
Relion
Byonic
REFMAC5

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