TY - JOUR
T1 - Antibody Binding Captures High Energy State of an Antigen
T2 - The Case of Nsp1 SARS-CoV-2 as Revealed by Hydrogen–Deuterium Exchange Mass Spectrometry
AU - Kant, Ravi
AU - Mishra, Nawneet
AU - Gross, Michael L.
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/12
Y1 - 2023/12
N2 - We describe an investigation using structural mass spectrometry (MS) of the impact of two antibodies, 15497 and 15498, binding the highly flexible SARS-CoV-2 Nsp1 protein. We determined the epitopes and paratopes involved in the antibody–protein interactions by using hydrogen–deuterium exchange MS (HDX-MS). Notably, the Fab (Fragment antigen binding) for antibody 15498 captured a high energy form of the antigen exhibiting significant conformational changes that added flexibility over most of the Nsp1 protein. The Fab for antibody 15497, however, showed usual antigen binding behavior, revealing local changes presumably including the binding site. These findings illustrate an unusual antibody effect on an antigen and are consistent with the dynamic nature of the Nsp1 protein. Our studies suggest that this interaction capitalizes on the high flexibility of Nsp1 to undergo conformational change and be trapped in a higher energy state by binding with a specific antibody.
AB - We describe an investigation using structural mass spectrometry (MS) of the impact of two antibodies, 15497 and 15498, binding the highly flexible SARS-CoV-2 Nsp1 protein. We determined the epitopes and paratopes involved in the antibody–protein interactions by using hydrogen–deuterium exchange MS (HDX-MS). Notably, the Fab (Fragment antigen binding) for antibody 15498 captured a high energy form of the antigen exhibiting significant conformational changes that added flexibility over most of the Nsp1 protein. The Fab for antibody 15497, however, showed usual antigen binding behavior, revealing local changes presumably including the binding site. These findings illustrate an unusual antibody effect on an antigen and are consistent with the dynamic nature of the Nsp1 protein. Our studies suggest that this interaction capitalizes on the high flexibility of Nsp1 to undergo conformational change and be trapped in a higher energy state by binding with a specific antibody.
KW - Nsp1
KW - antibody capture of high energy antigen
KW - epitope
KW - hydrogen–deuterium exchange
KW - mass spectrometry
KW - paratope
UR - http://www.scopus.com/inward/record.url?scp=85180726188&partnerID=8YFLogxK
U2 - 10.3390/ijms242417342
DO - 10.3390/ijms242417342
M3 - Article
C2 - 38139170
AN - SCOPUS:85180726188
SN - 1661-6596
VL - 24
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 24
M1 - 17342
ER -