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Cited by 0Protein Structure and DynamicsSARS-CoV-2 and COVID-19 ResearchSARS-CoV-2 detection and testing

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Met58 and di-acidic motif located at C-terminal region of SARS-CoV-2 ORF6 plays a crucial role in its structural conformations

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Kumar, Prateek, Saumya, Kumar Udit, Bhardwaj, Taniya, Giri, Rajanish·2025·Biophysical Chemistry
DOI 10.1016/j.bpc.2024.107384

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Abstract

Despite being mostly neglected in structural biology, the C-terminal Regions (CTRs) are studied to be multifunctional in humans as well as in viruses. Previously, SARS-CoV-2 Spike and NSP1 proteins' CTRs are observed to be disordered, and experimental evidence showed a gain of structure properties in different physiological environments. In this line, we have investigated the structural dynamics of CTR (residues 38-61) of SARS-CoV-2 ORF6 protein, disrupting bidirectional transport between the nucleus and cytoplasm. ORF6-CTR is disordered in nature but doesn't gain any structure in most conditions. As per studies, residue such as Methionine at 58th position in ORF6 is critical for interaction with Rae1-Nup98. Therefore, along with M58, we have identified a few other mutations from the literature and performed extensive structure modelling and dynamics studies using computational simulations. The exciting revelations in CTR models provide evidence of its structural flexibility and possible capabilities to perform multifunctionality inside the host.

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Research works printed but not linked: 23

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Metadata

Authors
Kumar, P., Saumya, K. U., Bhardwaj, T., & Giri, R.
Affiliations
Indian Institute of Technology Mandi (IN)
Corresponding author
Giri, Rajanish
ORCID
Venue
Biophysical Chemistry
Publisher
Elsevier BV
Published
2025-03
Volume
318
Pages
107384
ISSN
0301-4622 (ISSN-L)
DOI
10.1016/j.bpc.2024.107384
OpenAlex
W4405679875
Cited by
0
References
1
FWCI
0.00
Type
journal article
Language
en
Open access
Licence
Locations
  • Biophysical Chemistry (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Department of Science and Technology, Ministry of Science and Technology, India (SPARC/2018-2019/P37/SL, BT/11/IYBA/2018/06, CRG/2019/005603)
  • Indian Council of Medical Research (52/04/2020/BIO/BMS, 58/6/2020/PHA/BMS)
  • Ministry of Education, India (CRG/2019/005603, SPARC/2018-2019/P37/SL, BT/11/IYBA/2018/06)
  • Scheme for Promotion of Academic and Research Collaboration
  • Science and Engineering Research Board (BT/11/IYBA/2018/06, CRG/2019/005603)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
Keywords
C-terminal region, intrinsically disordered regions, protein structural dynamics, nuclear transport, protein structure modeling
MeSH terms
SARS-CoV-2, Humans, Methionine, Mutation, Protein Conformation, Viral Proteins, Amino Acid Motifs, Molecular Dynamics Simulation

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