A native prokaryotic voltage-dependent calcium channel with a novel selectivity filter sequence.

Area of Science:

• Biophysics
• Molecular Biology
• Biochemistry

Background:

• Voltage-dependent calcium channels (Cavs) are crucial for cellular processes.
• Prokaryotic voltage-dependent sodium channels (Navs) can be engineered for Ca²⁺ selectivity.
• Native prokaryotic Cavs were previously unidentified.

Purpose of the Study:

• To identify and characterize a native prokaryotic Cav.
• To elucidate the mechanism of Ca²⁺ selectivity in prokaryotic Cavs.
• To understand the evolutionary conservation of Ca²⁺ selectivity mechanisms.

Main Methods:

• Identification of a native prokaryotic Cav (CavMr).
• Site-directed mutagenesis to alter selectivity filter residues.
• Functional characterization of wild-type and mutant channels.

Main Results:

• The first native prokaryotic Cav, CavMr, was identified.
• CavMr's selectivity filter has fewer negative charges than artificial variants.
• A glycine residue in CavMr's filter is critical for Ca²⁺ selectivity.
• This glycine is conserved in eukaryotic Cav subdomains I and III.

Conclusions:

• A novel Ca²⁺ selectivity mechanism in prokaryotes was discovered.
• The findings offer insights into the conserved evolution of Ca²⁺ channels.
• This research bridges the understanding of prokaryotic and eukaryotic Cav function.