Expansion of the Major Facilitator Superfamily (MFS) to include novel transporters as well as transmembrane-acting enzymes

Wang, Steven C; Davejan, Pauldeen; Hendargo, Kevin J.; Javadi-Razaz, Ida; Chou, Amy; Yee, Daniel C.; Ghazi, Faezeh; Lam, Katie Jing Kay; Conn, Adam; Madrigal, Assael; Medrano-Soto, Arturo; Saier, Milton H.

doi:10.1016/j.bbamem.2020.183277

Cited by 48 publications

(41 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“… 28 The 11-TM topology has mostly arisen from a 12-TM ancestor that has lost the last TM segment. 29 The evolutionary and functional reason for this structural divergence in unclear.…”

Section: The Major Facilitator Superfamily (Mfs) Topologymentioning

confidence: 99%

Structures and General Transport Mechanisms by the Major Facilitator Superfamily (MFS)

et al. 2021

View full text Add to dashboard Cite

The major facilitator superfamily (MFS) is the largest known superfamily of secondary active transporters. MFS transporters are responsible for transporting a broad spectrum of substrates, either down their concentration gradient or uphill using the energy stored in the electrochemical gradients. Over the last 10 years, more than a hundred different MFS transporter structures covering close to 40 members have provided an atomic framework for piecing together the molecular basis of their transport cycles. Here, we summarize the remarkable promiscuity of MFS members in terms of substrate recognition and proton coupling as well as the intricate gating mechanisms undergone in achieving substrate translocation. We outline studies that show how residues far from the substrate binding site can be just as important for fine-tuning substrate recognition and specificity as those residues directly coordinating the substrate, and how a number of MFS transporters have evolved to form unique complexes with chaperone and signaling functions. Through a deeper mechanistic description of glucose (GLUT) transporters and multidrug resistance (MDR) antiporters, we outline novel refinements to the rocker-switch alternating-access model, such as a latch mechanism for proton-coupled monosaccharide transport. We emphasize that a full understanding of transport requires an elucidation of MFS transporter dynamics, energy landscapes, and the determination of how rate transitions are modulated by lipids.

show abstract

“… 28 The 11-TM topology has mostly arisen from a 12-TM ancestor that has lost the last TM segment. 29 The evolutionary and functional reason for this structural divergence in unclear.…”

Section: The Major Facilitator Superfamily (Mfs) Topologymentioning

confidence: 99%

Structures and General Transport Mechanisms by the Major Facilitator Superfamily (MFS)

et al. 2021

View full text Add to dashboard Cite

show abstract

“…For the MFS proteins in Pfam family MFS_1, two different evolutionary origins of sialic acid transporters were clearly identified (Fig. 3A), and a third origin was discovered uniquely in the MFS_2 family, which encompassed the GPH (Glycoside-Pentoside-Hexuronide:cation symporter) family [56, 57] (Fig. 3B).…”

Section: Resultsmentioning

confidence: 99%

Multiple evolutionary origins reflect the importance of sialic acid transporters in the colonisation potential of bacterial pathogens and commensals

Severi

Rudden

Bell

et al. 2021

Preprint

View full text Add to dashboard Cite

Located at the tip of cell surface glycoconjugates, sialic acids are at the forefront of host-microbe interactions and, being easily liberated by sialidase enzymes, are used as metabolites by numerous bacteria, particularly by pathogens and commensals living on or near diverse mucosal surfaces. These bacteria rely on specific transporters for the acquisition of host-derived sialic acids. Here, we present the first comprehensive genomic and phylogenetic analysis of bacterial sialic acid transporters, leading to the identification of multiple new families and subfamilies. Our phylogenetic analysis suggests that sialic acid-specific transport has evolved independently at least 8 times during the evolution of bacteria, from within 4 of the major families/superfamilies of bacterial transporters, and we propose a robust classification scheme to bring together a myriad of different nomenclatures that exist to date. The new transporters discovered occur in diverse bacteria including Spirochaetes, Bacteroidetes, Planctomycetes, and Verrucomicrobia, many of which are species that have not been previously recognised to have sialometabolic capacities. Two subfamilies of transporters stand out in being fused to the sialic acid mutarotase enzyme, NanM, and these transporter fusions are enriched in bacteria present in gut microbial communities. We also provide evidence for a possible function of a sialic acid transporter component in chemotaxis that is independent of transport. Our analysis supports the increasing experimental evidence that competition for host-derived sialic acid is a key phenotype for successful colonisation of complex mucosal microbiomes, such that a strong evolutionary selection has occurred for the emergence of sialic acid specificity within existing transporter architectures.

show abstract

“…The genome of filamentous fungi encodes numerous MFS transporters [79,80] divided across 17 families. Comprising of a single polypeptide, families 1, 5, and 7 transport sugars, such as pentoses and hexoses inside the cell [81][82][83] through a mechanism that uses free energy obtained from a chemiosmotic ion gradient [77,84]. MFS transporters translocate also nucleosides, lipids, amino acids, peptides, and ions [84].…”

Section: Discussionmentioning

confidence: 99%

“…Comprising of a single polypeptide, families 1, 5, and 7 transport sugars, such as pentoses and hexoses inside the cell [81][82][83] through a mechanism that uses free energy obtained from a chemiosmotic ion gradient [77,84]. MFS transporters translocate also nucleosides, lipids, amino acids, peptides, and ions [84]. The main feature of MFS transporters in filamentous fungi is their ability to sense and carry more than one kind of sugar [67].…”

Section: Discussionmentioning

confidence: 99%

Effect of Oligosaccharide Degree of Polymerization on the Induction of Xylan-Degrading Enzymes by Fusarium oxysporum f. sp. Lycopersici

2020

View full text Add to dashboard Cite

Xylan is one of the most abundant carbohydrates on Earth. Complete degradation of xylan is achieved by the collaborative action of endo-β-1,4-xylanases and β-d-xylosidases and a number of accessories enzymes. In filamentous fungi, the xylanolytic system is controlled through induction and repression. However, the exact mechanism remains unclear. Substrates containing xylan promote the induction of xylanases, which release xylooligosaccharides. These, in turn, induce expression of xylanase-encoding genes. Here, we aimed to determine which xylan degradation products acted as inducers, and whether the size of the released oligomer correlated with its induction strength. To this end, we compared xylanase production by different inducers, such as sophorose, lactose, cellooligosaccharides, and xylooligosaccharides in Fusarium oxysporum f. sp. lycopersici. Results indicate that xylooligosaccharides are more effective than other substrates at inducing endoxylanase and β-xylosidases. Moreover, we report a correlation between the degree of xylooligosaccharide polymerization and induction efficiency of each enzyme. Specifically, xylotetraose is the best inducer of endoxylanase, xylohexaose of extracellular β-xylosidase, and xylobiose of cell-bound β-xylosidase.

show abstract

Expansion of the Major Facilitator Superfamily (MFS) to include novel transporters as well as transmembrane-acting enzymes

Cited by 48 publications

References 89 publications

Structures and General Transport Mechanisms by the Major Facilitator Superfamily (MFS)

Structures and General Transport Mechanisms by the Major Facilitator Superfamily (MFS)

Multiple evolutionary origins reflect the importance of sialic acid transporters in the colonisation potential of bacterial pathogens and commensals

Effect of Oligosaccharide Degree of Polymerization on the Induction of Xylan-Degrading Enzymes by Fusarium oxysporum f. sp. Lycopersici

Contact Info

Product

Resources

About