Structural polymorphism of coiled-coils from the stalk domain of SARS-CoV-2 spike protein

Živič, Zala (author), Strmšek, Žiga (author), Novinec, Marko (author), Lah, Jurij (author), Hadži, San (author)

Spike trimer plays a key role in SARS-CoV-2 infection and vaccine development. It consists of a globular head and a flexible stalk domain that anchors the protein into the viral membrane. While the head domain has been extensively studied, the properties of the adjoining stalk are poorly understood. Here, we characterize the coiled-coil formation and thermodynamic stability of the stalk domain and its segments. We find that the N-terminal segment of the stalk does not form coiled-coils and remains disordered in solution. The C-terminal stalk segment forms a trimeric coiled-coil in solution, which becomes significantly stabilized in the context of the full-length stalk. Its crystal structure reveals a novel antiparallel tetramer coiled-coil with an unusual combination of a-d and e-a-d hydrophobic core packing. Structural analysis shows that a subset of hydrophobic residues stabilizes different coiled-coil structures: trimer, tetramer, and heterohexamer, underscoring a highly polymorphic nature of the SARS-CoV-2 stalk sequence.

• Language: English
• Keywords: spike protein, corona virus, coiled-coil, SARS-CoV-2, spike, thermodynamics, X-ray
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Publication status: Published
• Publication version: Version of Record
• Year: 2022
• Number of pages: 11 str.
• Numbering: Vol. 36, iss. 3, art. e22199
• PID: 20.500.12556/RUL-136995
• UDC: 577.322
• ISSN on article: 0892-6638
• DOI: 10.1096/fj.202101670R
• COBISS.SI-ID: 97817859
• Publication date in RUL: 27.05.2022

Record is a part of a journal

• Title: The FASEB journal
• Shortened title: FASEB j.
• Publisher: Wiley, Federation of American Societies for Experimental Biology
• ISSN: 0892-6638
• COBISS.SI-ID: 25451520

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

• Language: Slovenian
• Keywords: protein spike, korona virus, obvita vijačnica