Work

Engineering selectivity into RGK GTPase inhibition of voltage-dependent calcium channels

Year: 2018

Type: article

Abstract: Significance Influx of calcium ions through surface membrane calcium channels that open in response to electrical signals is important for vital biological processes including generation of the heartbeat and nerve cell communication. Blocking such calcium channels in a tissue- and isoform-specific manner is a sought-after treatment strategy for diseases including chronic pain and Parkinson’s disease. Proteins that can be expressed in cells to selectively block different calcium channel types have particular advantages over conventional small-molecule blockers. A four-member family of proteins known as RGK proteins strongly inhibit calcium channels, but do so in a non-selective manner, limiting their potential usefulness. Here we identified mutated RGK proteins that perform as isoform-selective calcium channel blockers, advancing the therapeutic potential of these proteins.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.1811024115

Authors: Akil A. Puckerin, Donald D. Chang, Zunaira Shuja, Papiya Choudhury, Joachim Scholz, Henry M. Colecraft

Institutions: Columbia University, Columbia University Irving Medical Center

Language: English

Topic: Ion channel regulation and function

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Funders: American Heart Association, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences