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Vitamin C and Vitamin D3 show strong binding with the amyloidogenic region of G555F mutant of Fibrinogen A alpha-chain associated with renal amyloidosis: proposed possible therapeutic intervention

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Abstract

G555F mutant of Fibrinogen A alpha-chain (FGA) is reported to be associated with kidney amyloidosis. In the current study, we have modelled the G555F mutant and examined the mutation’s effect on the structural and functional level. We have also docked Vitamin C and D3 on the mutant’s amyloidogenic region to identify if these vitamins can bind amyloidogenic regions. Further, we analyzed if they could prevent or modulate amyloid formation by stopping critical interactions in amyloidogenic regions in FGA. We used the wild type FGA model protein as a control. Our docking and molecular dynamics simulation results indicate stronger Vitamin D3 binding than Vitamin C to the amyloidogenic region of the mutant protein. The RMSD, radius of gyration, and RMSF values were higher for the G555F mutant than the FGA wild type protein. Overall, the results support these vitamins’ potential as a therapeutic and anti-amyloidogenic agent for FGA renal amyloidosis.

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Acknowledgement

The infrastructure provided by the Department of Biochemistry, Institute of Medical Sciences, BHU is acknowledged. Financial support by DST, Government of India in the form of Woman Scientist A (WoS-A) research grant [Project no: SR/WOS-A/ LS-478-2017] to MP is also acknowledged. DK acknowledges the research fellowship provided by IIT-BHU. The support and the resources provided by the PARAM Shivay Facility under the National Supercomputing Mission, Government of India at the Indian Institute of Technology, Varanasi are gratefully acknowledged.

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Authors and Affiliations

  1. Department of Biochemistry, Institute of Medical Science, Banaras Hindu University, Varanasi, 221005, India

    Monu Pande & Ragini Srivastava

  2. School of Biochemical Engineering, Indian Institute of Technology (BHU), Varanasi, 221005, India

    Debanjan Kundu

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  2. Debanjan Kundu
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Contributions

Monu Pande contributed to conceptualisation, validation, formal analysis, resources (docking, simulation, and analysis) writing—original draft, Debanjan Kundu was involved in methodology, resources (docking, simulation, and analysis), and writing—original draft, and Ragini Srivastava contributed to writing, review and editing, and supervision.

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Correspondence to Ragini Srivastava.

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Pande, M., Kundu, D. & Srivastava, R. Vitamin C and Vitamin D3 show strong binding with the amyloidogenic region of G555F mutant of Fibrinogen A alpha-chain associated with renal amyloidosis: proposed possible therapeutic intervention. Mol Divers 26, 939–949 (2022). https://doi.org/10.1007/s11030-021-10205-7

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