TY - JOUR

T1 - Structure and Orientation of the SARS-Coronavirus-2 Spike Protein at Air-Water Interfaces

AU - Bregnhøj, Mikkel

AU - Roeters, Steven J.

AU - Chatterley, Adam S.

AU - Madzharova, Fani

AU - Mertig, Rolf

AU - Pedersen, Jan Skov

AU - Weidner, Tobias

N1 - Funding Information: This article is part of a project that has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (Grant agreement no. 819039 F-BioIce). T.W. acknowledges support by the Novo Nordisk Foundation (Facility Grant NanoScat, no. NNF18OC0032628). Publisher Copyright: ©

PY - 2022/5/12

Y1 - 2022/5/12

N2 - The SARS coronavirus 2 (SARS-CoV-2) spike protein is located at the outermost perimeter of the viral envelope and is the first component of the virus to make contact with surrounding interfaces. The stability of the spike protein when in contact with surfaces plays a deciding role for infection pathways and for the viability of the virus after surface contact. While cryo-EM structures of the spike protein have been solved with high resolution and structural studies in solution have provided information about the secondary and tertiary structures, only little is known about the folding when adsorbed to surfaces. We here report on the secondary structure and orientation of the S1 segment of the spike protein, which is often used as a model protein for in vitro studies of SARS-CoV-2, at the air-water interface using surface-sensitive vibrational sum-frequency generation (SFG) spectroscopy. The air-water interface plays an important role for SARS-CoV-2 when suspended in aerosol droplets, and it serves as a model system for hydrophobic surfaces in general. The SFG experiments show that the S1 segment of the spike protein remains folded at the air-water interface and predominantly binds in its monomeric state, while the combination of small-angle X-ray scattering and two-dimensional infrared spectroscopy measurements indicate that it forms hexamers with the same secondary structure in aqueous solution.

AB - The SARS coronavirus 2 (SARS-CoV-2) spike protein is located at the outermost perimeter of the viral envelope and is the first component of the virus to make contact with surrounding interfaces. The stability of the spike protein when in contact with surfaces plays a deciding role for infection pathways and for the viability of the virus after surface contact. While cryo-EM structures of the spike protein have been solved with high resolution and structural studies in solution have provided information about the secondary and tertiary structures, only little is known about the folding when adsorbed to surfaces. We here report on the secondary structure and orientation of the S1 segment of the spike protein, which is often used as a model protein for in vitro studies of SARS-CoV-2, at the air-water interface using surface-sensitive vibrational sum-frequency generation (SFG) spectroscopy. The air-water interface plays an important role for SARS-CoV-2 when suspended in aerosol droplets, and it serves as a model system for hydrophobic surfaces in general. The SFG experiments show that the S1 segment of the spike protein remains folded at the air-water interface and predominantly binds in its monomeric state, while the combination of small-angle X-ray scattering and two-dimensional infrared spectroscopy measurements indicate that it forms hexamers with the same secondary structure in aqueous solution.

KW - CONFORMATION

KW - PACKING

KW - PEPTIDES

KW - SPECTROSCOPY

KW - SUM-FREQUENCY GENERATION

KW - COVID-19

KW - SARS-CoV-2

KW - Humans

KW - Spike Glycoprotein, Coronavirus/chemistry

KW - Water/chemistry

UR - http://www.scopus.com/inward/record.url?scp=85130001048&partnerID=8YFLogxK

U2 - 10.1021/acs.jpcb.2c01272

DO - 10.1021/acs.jpcb.2c01272

M3 - Journal article

C2 - 35477296

AN - SCOPUS:85130001048

VL - 126

SP - 3425

EP - 3430

JO - Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces & Biophysical

JF - Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces & Biophysical

SN - 1520-6106

IS - 18

ER -