Phylogenetic and conservation analyses of MFS transporters

Abstract

Major facilitator superfamily is one of the largest superfamily of secondary transporters present across the kingdom of life. Considering the physiological and clinical importance of MFS proteins, we attempted to explore the phylogenetic and structural aspects of the superfamily. To achieve the objectives, we performed global sequence-based analyses of MFS proteins encompassing multiple taxa. Notably, phylogenetic analysis of MFS proteins resulted in the clustering of MFS proteins based on their function, rather than lineage of the respective organisms. Additionally, we employed information theoretic measures, Relative entropy (RE) and Cumulative relative entropy (CRE) to decipher fold-specific and function-specific residues, respectively, in the MFS proteins. The residues with high RE score when mapped on to the 3D-structure of MFS transporter LacY, were found to be distributed throughout the tertiary structure of the protein. On the other hand, CRE calculation was employed to contrast two subfamilies Drug H + antiporter 1 and 3 (DHA1 and DHA3). The particular analysis unveiled certain differentially conserved residues in DHA1 as compared to DHA3 highlighting family-specific importance of them. Remarkably, a number of high scoring CRE residues have already established functional roles, for instance, the arginine residue present in TMH4. Altogether, the current study apart from providing an insight into the functional clustering of MFS proteins also identifies residues with established or plausible roles in the transport mechanism. Thus, the study lays a platform for future structure-function studies of these proteins.

A guide to plasma membrane solute carrier proteins

“…The number of transmembrane domains was obtained from Uniprot and literature cited in the respective sections. This table was assembled using information from [36] and [559]. For more specific structural information for these protein families, the reader is referred to Bai et al [36].…”

Glucose Availability Alters Gene and Protein Expression of Several Newly Classified and Putative Solute Carriers in Mice Cortex Cell Culture and D. melanogaster

“…Many transporter proteins are highly conserved and while the exact distribution and localization might not be the same across species, the function is more often conserved. Phylogenetic analysis of transporters belonging to the MFS result in function based clustering rather than lineage based (Vishwakarma et al, 2018). GLUT1 is also responsible for glucose uptake in Drosophila melanogaster, however, not across the BBB as in humans, but rather into neurons in the brain (Volkenhoff et al, 2018).…”

In Silico Predictions of Ecological Plasticity Mediated by Protein Family Expansions in Early-Diverging Fungi

“…We found that protein families, which have previously attracted attention, have dynamic evolutionary histories reflecting their adaptive potential towards new ecological challenges. Among others, ABC and MFS transporters, which enable resistance against multiple environmental threats [152,153], are proteins involved in fungal cell wall biosynthesis such as chitin synthases (GT2) essential for interactions with other organisms and fungal defence [47]. Nutritional mode has a profound impact on the evolution of fungal genomes and the majority of differentially represented protein families in fungal proteomes are indeed associated with the digestion of nutrients (e.g., chitinases GH19 in fungi living with insects and loss of acetyl-xylan esterases CE2 and CE6 in endomycorrhizal Glomeromycota).…”