Identification of determinants of lipid and ion transport in TMEM16/anoctamin proteins through a Bayesian statistical analysis

Abstract

The TMEM16/Anoctamin protein family (TMEM16x) is composed of members with different functions; some members form Ca²⁺-activated chloride channels, while others are lipid scramblases or combine the two functions. TMEM16x proteins are typically activated in response to agonist-induced rises of intracellular Ca²⁺; thus, they couple Ca²⁺-signalling with cell electrical activity or plasmalemmal lipid homeostasis. The structural domains underlying these functions are not fully defined. We used a Naïve Bayes classifier to gain insights into these domains. The method enabled identification of regions involved in either ion or lipid transport, and suggested domains for possible pharmacological exploitation. The method allowed the prediction of the transport property of any given TMEM16x. We envisage this strategy could be exploited to illuminate the structure-function relationship of any protein family composed of members playing different molecular roles.

Keywords: Anoctamins; Lipid scramblases; Pharmacology; TMC-1; TMEM16 proteins; TMEM16A.