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Blocking the interface region amongst S100A6 and RAGE V domain via S100B protein

Sung, Hsin-Yen ; Dowarha, Deepu ; Chou, Ruey-Hwang ; Yu, Chin

Biochemical and biophysical research communications, 2020-12, Vol.533 (3), p.332-337 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
Blocking the interface region amongst S100A6 and RAGE V domain via S100B protein
Autor: Sung, Hsin-Yen ; Dowarha, Deepu ; Chou, Ruey-Hwang ; Yu, Chin
Assuntos: Binding Sites ; Cell Cycle Proteins - chemistry ; Cell Cycle Proteins - genetics ; Cell Cycle Proteins - metabolism ; Cell Cycle Proteins - pharmacology ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Cloning, Molecular ; Epithelial Cells - drug effects ; Epithelial Cells - metabolism ; Epithelial Cells - pathology ; Escherichia coli - genetics ; Escherichia coli - metabolism ; Gene Expression Regulation, Neoplastic ; Genetic Vectors - chemistry ; Genetic Vectors - metabolism ; HADDOCK ; Humans ; Molecular Docking Simulation ; NMR Spectroscopy ; Nuclear Magnetic Resonance, Biomolecular ; Protein Binding ; Protein Conformation, alpha-Helical ; Protein Conformation, beta-Strand ; Protein Interaction Domains and Motifs ; Protein Multimerization ; RAGE ; Receptor for Advanced Glycation End Products - chemistry ; Receptor for Advanced Glycation End Products - genetics ; Receptor for Advanced Glycation End Products - metabolism ; Recombinant Proteins - chemistry ; Recombinant Proteins - genetics ; Recombinant Proteins - metabolism ; Recombinant Proteins - pharmacology ; S100 Calcium Binding Protein A6 - chemistry ; S100 Calcium Binding Protein A6 - genetics ; S100 Calcium Binding Protein A6 - metabolism ; S100 Calcium Binding Protein A6 - pharmacology ; S100 Calcium Binding Protein beta Subunit - chemistry ; S100 Calcium Binding Protein beta Subunit - genetics ; S100 Calcium Binding Protein beta Subunit - metabolism ; S100 Calcium Binding Protein beta Subunit - pharmacology ; S100A6 ; S100B ; WST-1
É parte de: Biochemical and biophysical research communications, 2020-12, Vol.533 (3), p.332-337
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descrição: The Ca2+-mediated S100 family protein S100A6 has a crucial task in various intracellular and extracellular activities thereby demonstrating a possible involvement in the advancement and development of malignant tumors. S100A6 has been found to associate with receptor for advanced glycation end products, RAGE, through its extracellular extension. This extension is famously identified as a prominent receptor for many S100 family associates. Additionally, S100A6 binds to S100B protein and forms a heterodimer. Thus, we consider the S100B protein to be a prospective drug molecule to obstruct the interacting regions amongst S100A6 and RAGE V domain. We applied the NMR spectroscopy method to locate the binding area amid the S100A6m (mutant S100A6, cysteine at 3rd position of S100A6 is replaced with serine, C3S) and S100B proteins. The 1H–15N HSQC NMR titrations revealed the probable requisite dynamics of S100A6m and S100B interfaces. Utilizing data from the NMR titrations as input parameters, we ran the HADDOCK program and created a S100A6m-S100B heterodimer complex. The obtained complex was then superimposed with the reported complex of S100A6m-RAGE V domain. This superimposition displayed the possibility of S100B to be a potential antagonist that can block the interface area of the S100A6m and the RAGE V domain. Moreover, an in vitro cancer model using SW480 cells in water-soluble tetrazolium-1 assay (WST-1) showed a noticeable change in the cell proliferation as an effect of these proteins. Our study indicates the possibility to develop a S100B-like competitor that could play a key role in the treatment of S100- and RAGE-mediated human diseases. •S100A6m and S100B protein interacts with each other.•S100A6m and S100B forms a heterodimer complex successfully.•S100B blocks the interaction between S100A6m and RAGE-V.•S100B interfering with the interaction of S100A6m and RAGE-V domain is demonstrated by the WST-1 assay in vitro using SW480 Cells.
Editor: United States: Elsevier Inc
Idioma: Inglês

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Blocking the interface region amongst S100A6 and RAGE V domain via S100B protein

Sung, Hsin-Yen ; Dowarha, Deepu ; Chou, Ruey-Hwang ; Yu, Chin

United States: Elsevier Inc

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