Calcium channel protein Cch1 (Cch1)

Calcium channel protein Cch1 is a fungal-specific integral membrane protein that functions as the pore-forming subunit of the high-affinity calcium uptake system (HACS) [1][2]. It is a structural and functional homolog of the alpha-1 subunit found in mammalian voltage-gated calcium channels, although it exhibits distinct regulatory properties and sequence variations [3]. Cch1 operates in a complex with the regulatory protein Mid1 to mediate calcium influx in response to various environmental stressors, including alkaline pH, cold stress, and low calcium availability [4]. In pathogenic fungi such as Candida albicans and Cryptococcus neoformans, Cch1 is a critical factor for virulence, survival within the host environment, and the development of resistance to antifungal drugs [4][5]. Because of its essential role in fungal physiology and its divergence from human calcium channels, Cch1 is considered a promising target for the development of novel, non-toxic antifungal therapeutics [5][6]. Inhibition of Cch1 disrupts vital calcium-dependent signaling pathways, such as the calcineurin-Crz1 pathway, which leads to impaired cell wall integrity and increased susceptibility to existing antifungal agents like azoles [6][7]. Research has shown that various classical calcium channel blockers, such as Verapamil, can inhibit Cch1-mediated calcium entry, providing a template for the design of more selective fungal calcium channel inhibitors [5][8]. [1] UniProt (P53048); [2] Paidhungat, M. & Garrett, S. (1997) PMID: 9381187; [3] Peiter, E., et al. (2005) PMID: 16166549; [4] Liu, S., et al. (2015) PMID: 26038221; [5] Edlind, T. D., et al. (2002) PMID: 12384351; [6] Teng, L., et al. (2013) PMID: 23610427; [7] Cyert, M. S. (2003) PMID: 12783569; [8] Yu, Q., et al. (2014) PMID: 25150596.

Other names

Cch1pVoltage-gated calcium channel subunit Cch1Calcium channel protein 1YGR217W

Inhibition of calcium influx through the high-affinity calcium uptake system (HACS) to disrupt calcium-dependent signaling pathways essential for fungal growth and virulence.