• 제목/요약/키워드: Receptor binding motif (RBM)

검색결과 4건 처리시간 0.02초

SARS-CoV-2 Delta (B.1.617.2) Variant: A Unique T478K Mutation in Receptor Binding Motif (RBM) of Spike Gene

  • Hyunjhung Jhun;Ho-Young Park;Yasmin Hisham;Chang-Seon Song;Soohyun Kim
    • IMMUNE NETWORK
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    • 제21권5호
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    • pp.32.1-32.14
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    • 2021
  • Over two hundred twenty-eight million cases of coronavirus disease 2019 (COVID-19) in the world have been reported until the 21st of September 2021 after the first rise in December 2019. The virus caused the disease called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Over 4 million deaths blame COVID-19 during the last one year and 8 months in the world. Currently, four SARS-CoV-2 variants of concern are mainly focused by pandemic studies with limited experiments to translate the infectivity and pathogenicity of each variant. The SARS-CoV-2 α, β, γ, and δ variant of concern was originated from United Kingdom, South Africa, Brazil/Japan, and India, respectively. The classification of SARS-CoV-2 variant is based on the mutation in spike (S) gene on the envelop of SARS-CoV-2. This review describes four SARS-CoV-2 α, β, γ, and δ variants of concern including SARS-CoV-2 ε, ζ, η, ι, κ, and B.1.617.3 variants of interest and alert. Recently, SARS-CoV-2 δ variant prevails over different countries that have 3 unique mutation sites: E156del/R158G in the N-terminal domain and T478K in a crucial receptor binding domain. A particular mutation in the functional domain of the S gene is probably associated with the infectivity and pathogenesis of the SARS-CoV-2 variant.

Aryl Sulfonamides Induce Degradation of Aryl Hydrocarbon Receptor Nuclear Translocator through CRL4DCAF15 E3 Ligase

  • Kim, Sung Ah;Jo, Seung-Hyun;Cho, Jin Hwa;Yu, Min Yeong;Shin, Ho-Chul;Kim, Jung-Ae;Park, Sung Goo;Park, Byoung Chul;Kim, Sunhong;Kim, Jeong-Hoon
    • Molecules and Cells
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    • 제43권11호
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    • pp.935-944
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    • 2020
  • Aryl hydrocarbon receptor nuclear translocator (ARNT) plays an essential role in maintaining cellular homeostasis in response to environmental stress. Under conditions of hypoxia or xenobiotic exposure, ARNT regulates the subset of genes involved in adaptive responses, by forming heterodimers with hypoxia-inducible transcription factors (HIF1α and HIF2α) or aryl hydrocarbon receptor (AhR). Here, we have shown that ARNT interacts with DDB1 and CUL4-associated factor 15 (DCAF15), and the aryl sulfonamides, indisulam and E7820, induce its proteasomal degradation through Cullin-RING finger ligase 4 containing DCAF15 (CRL4DCAF15) E3 ligase. Moreover, the two known neo-substrates of aryl sulfonamide, RNA-binding motif protein 39 (RBM39) and RNA-binding motif protein 23 (RBM23), are not required for ARNT degradation. In line with this finding, aryl sulfonamides inhibited the transcriptional activities of HIFs and AhR associated with ARNT. Our results collectively support novel regulatory roles of aryl sulfonamides in both hypoxic and xenobiotic responses.

Receptor binding motif surrounding sites in the Spike 1 protein of infectious bronchitis virus have high susceptibility to mutation related to selective pressure

  • Seung-Min Hong;Seung-Ji Kim;Se-Hee An;Jiye Kim;Eun-Jin Ha;Howon Kim;Hyuk-Joon Kwon;Kang-Seuk Choi
    • Journal of Veterinary Science
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    • 제24권4호
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    • pp.51.1-51.17
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    • 2023
  • Background: To date, various genotypes of infectious bronchitis virus (IBV) have co-circulated and in Korea, GI-15 and GI-19 lineages were prevailing. The spike protein, particularly S1 subunit, is responsible for receptor binding, contains hypervariable regions and is also responsible for the emerging of novel variants. Objective: This study aims to investigate the putative major amino acid substitutions for the variants in GI-19. Methods: The S1 sequence data of IBV isolated from 1986 to 2021 in Korea (n = 188) were analyzed. Sequence alignments were carried out using Multiple alignment using Fast Fourier Transform of Geneious prime. The phylogenetic tree was generated using MEGA-11 (ver. 11.0.10) and Bayesian analysis was performed by BEAST v1.10.4. Selective pressure was analyzed via online server Datamonkey. Highlights and visualization of putative critical amino acid were conducted by using PyMol software (version 2.3). Results: Most (93.5%) belonged to the GI-19 lineage in Korea, and the GI-19 lineage was further divided into seven subgroups: KM91-like (Clade A and B), K40/09-like, QX-like (I-IV). Positive selection was identified at nine and six residues in S1 for KM91-like and QX-like IBVs, respectively. In addition, several positive selection sites of S1-NTD were indicated to have mutations at common locations even when new clades were generated. They were all located on the lateral surface of the quaternary structure of the S1 subunits in close proximity to the receptor-binding motif (RBM), putative RBM motif and neutralizing antigenic sites in S1. Conclusions: Our results suggest RBM surrounding sites in the S1 subunit of IBV are highly susceptible to mutation by selective pressure during evolution.

SARS-CoV-2 Omicron Mutation Is Faster than the Chase: Multiple Mutations on Spike/ACE2 Interaction Residues

  • Sinae Kim;Tam T. Nguyen;Afeisha S. Taitt;Hyunjhung Jhun;Ho-Young Park;Sung-Han Kim;Yong-Gil Kim;Eun Young Song;Youngmin Lee;Hokee Yum;Kyeong-Cheol Shin;Yang Kyu Choi;Chang-Seon Song;Su Cheong Yeom;Byoungguk Kim;Mihai Netea;Soohyun Kim
    • IMMUNE NETWORK
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    • 제21권6호
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    • pp.38.1-38.8
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    • 2021
  • Recently, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (B.1.1.529) Omicron variant originated from South Africa in the middle of November 2021. SARS-CoV-2 is also called coronavirus disease 2019 (COVID-19) since SARS-CoV-2 is the causative agent of COVID-19. Several studies already suggested that the SARS-CoV-2 Omicron variant would be the fastest transmissible variant compared to the previous 10 SARS-CoV-2 variants of concern, interest, and alert. Few clinical studies reported the high transmissibility of the Omicron variant but there is insufficient time to perform actual experiments to prove it, since the spread is so fast. We analyzed the SARS-CoV-2 Omicron variant, which revealed a very high rate of mutation at amino acid residues that interact with angiostatin-converting enzyme 2. The mutation rate of COVID-19 is faster than what we prepared vaccine program, antibody therapy, lockdown, and quarantine against COVID-19 so far. Thus, it is necessary to find better strategies to overcome the current crisis of COVID-19 pandemic.