Exploring human sperm nuclear basic protein-DNA interactions: could hexavalent chromium play an interfering role?

Area of Science:

• Biochemistry
• Reproductive Biology
• Toxicology

Background:

• Sperm nuclear basic proteins (SNBP), mainly protamines, are crucial for DNA packaging and male fertility.
• Arginine residues in SNBP mediate DNA interaction via salt bridges.
• Hexavalent chromium [Cr(VI)] is a known reproductive toxicant.

Purpose of the Study:

• To investigate the impact of Cr(VI) on SNBP-DNA binding.
• To elucidate the role of arginine integrity in SNBP-DNA interactions under chromium exposure.
• To understand the molecular mechanisms of chromium-induced reproductive toxicity.

Main Methods:

• Electrophoretic mobility shift assays (EMSA) to assess SNBP-DNA complex formation.
• SDS-PAGE and native-PAGE to analyze SNBP aggregation.
• Fluorescence spectroscopy to study surface polar exposition changes.
• Deguanidination of SNBP with hydrazine.
• In silico molecular docking to model Cr(III)-arginine and Cr(III)-DNA interactions.

Main Results:

• Cr(VI) treatment significantly impaired SNBP-DNA complex formation and induced SNBP aggregation.
• Deguanidination of SNBP mimicked Cr(VI) effects on DNA binding.
• Cr(III) forms coordination complexes with arginine guanidinium groups, disrupting DNA binding.
• Cr(III) exhibits preferential binding to guanine in GC-rich DNA sequences.

Conclusions:

• Arginine integrity is essential for proper SNBP-DNA binding and sperm chromatin organization.
• Cr(VI)-induced genotoxicity in sperm is mediated by its reduced form, Cr(III), binding to arginine residues.
• Disruption of SNBP-DNA binding by chromium affects human reproductive health.