7DK0

Crystal structure of SARS-CoV-2 Spike RBD in complex with MW05 Fab

Summary for 7DK0

• Entry DOI: 10.2210/pdb7dk0/pdb
• Related: 7DJZ
• Descriptor: MW05 heavy chain, MW05 light chain, Spike protein S1, ... (4 entities in total)
• Functional Keywords: sars-cov-2, spike, rbd, antibody, ade, virus, immune system-viral protein complex, immune system/viral protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 72156.69

Authors

Wang, J.,Jiao, S.,Wang, R.,Zhang, J.,Zhang, M.,Wang, M. (deposition date: 2020-11-22, release date: 2021-06-09, Last modification date: 2023-11-29)

Primary citation

Wang, S.,Wang, J.,Yu, X.,Jiang, W.,Chen, S.,Wang, R.,Wang, M.,Jiao, S.,Yang, Y.,Wang, W.,Chen, H.,Chen, B.,Gu, C.,Liu, C.,Wang, A.,Wang, M.,Li, G.,Guo, C.,Liu, D.,Zhang, J.,Zhang, M.,Wang, L.,Gui, X.
Antibody-dependent enhancement (ADE) of SARS-CoV-2 pseudoviral infection requires Fc gamma RIIB and virus-antibody complex with bivalent interaction.
Commun Biol, 5:262-262, 2022

PubMed Abstract: Understanding the underlying molecular mechanisms behind ADE of SARS-CoV-2 is critical for development of safe and effective therapies. Here, we report that two neutralizing mAbs, MW01 and MW05, could enhance the infection of SARS-CoV-2 pseudovirus on FcγRIIB-expressing B cells. X-ray crystal structure determination and S trimer-binding modeling showed that MW01 and MW05 could bind to RBDs in S trimer with both "up" and "down" states. While, the neutralizing mAb MW07, which has no ADE activity only binds to RBD in S trimer with "up" state. Monovalent MW01 and MW05 completely diminished the ADE activity compared with their bivalent counterparts. Moreover, both macropinocytosis and endocytosis are confirmed involving in ADE of SARS-CoV-2 pseudoviral infection. Blocking endosome transportation and lysosome acidification could inhibit the ADE activity mediated by MW05. Together, our results identified a novel ADE mechanism of SARS-CoV-2 pseudovirus in vitro, FcγRIIB-mediated uptake of SARS-CoV-2/mAb complex with bivalent interaction.

PubMed: 35332252
DOI: 10.1038/s42003-022-03207-0

Experimental method

X-RAY DIFFRACTION (3.199 Å)