Many mechanistic aspects of solute transport across membranes, from the ion-substrate coupling to the individual steps of the transport cycle, are still unresolved for most members of the SoLute Carriers (SLC) superfamily. The appearance of an increasing number of structures begins to provide the conformational framework for understanding these processes. The best characterized families, the amino acids and neurotransmitter transporters from the SLC1 and SLC6 families seem to share their translocation mechanism with an increasing number of other SLC transporter families. Similarities and differences in structure, sequences and functional properties between transporters are an interesting source of information for structure function studies. 3D structures give a more precise idea on the architecture of these proteins and suggest specific role/s for individual amino acids. To associate the transporter structure with its function implies identifying suitable model systems and methods for investigating the time lapse of the transport event, characterizing their selectivity and quantifying their energy profile in biological membranes. The increasing availability of novel crystal structures, modern molecular modelling data, bioinformatics analysis, comparative and deep functional analysis in combination with the already available data are significantly accelerating the discovery of the key regions/amino acids in SLC transporters. This is leading to a better understanding of interaction with substrates, the action of inhibitors, the translocation steps, etc. which will help to fully comprehend the role of transporters in both physiological and pathological conditions and/or to develop new drugs.
Hundreds of transporters from different SLC subfamilies are expressed on the membranes of almost all living organisms, where they contribute to cell homeostasis by regulating the passage across the cells of neurotransmitters, nutrients, ions, etc. In current membrane transporters research, the study of the bacterial homologs strongly supports the advances in knowledge of the structural biology of the human transporters, and such distant ortholog proteins often result extremely important for e.g. the detailed understanding of a translocation mechanism. Studying closer orthologues of human SLC genes from less conventional (i.e. non-mammalian, non-bacterial) species together with comparing their sequences with the human members of the same family often represents a smart and low-cost alternative to identify amino acid residue(s) conserved in strategic positions during evolution. This helps in e.g. creating specific mutants of (a) human protein(s) to address their function by defining the role of single amino acids and/or functional regions. Conversely, small or large differences in aligned sequences can be correlated to significant differences in functionality, thus helping to increase our knowledge in transporter physiology, in drug interaction and in understanding the molecular basis of certain diseases and disorders.
The present collection is aimed to join contributions that discuss structure-function relationships in the SLC transporters with particular focus on substrate(s)-transporter(s) binding, inhibitor(s)-transporter(s) interactions, ion(s)-substrate(s) coupling, steps of the transport cycles, etc. The use of comparative approaches highlighting the function of transporters isolated from less conventional models such as lower vertebrates (amphibians, fishes, etc.), invertebrates (fruit flies, nematodes, etc.), lower metazoans (jellyfishes, etc.) and/or simple eukaryotes (yeasts, etc.) will be appreciated. A multidisciplinary approach that combines e.g. in silico modelling with structure-function in vitro and in vivo, finding the appropriate model for a transport system, could be a type of contribution to include in this present collection. We welcome submissions related to the following sub-topics:
• Structure-function relationships
• Mechanisms of transport
• Transport regulation in physiology and pathology
• Transporters: substrate, inhibitors and drug interaction
• Drug transport and transporters
• Experimental methods in SLC investigation
• Genomic research for new SLC transporters discovery
• Models of transport process
• Biophysical characterization of SLC proteins
• Bioinformatics and novel tools and methods to analyze SLC transporters
Many mechanistic aspects of solute transport across membranes, from the ion-substrate coupling to the individual steps of the transport cycle, are still unresolved for most members of the SoLute Carriers (SLC) superfamily. The appearance of an increasing number of structures begins to provide the conformational framework for understanding these processes. The best characterized families, the amino acids and neurotransmitter transporters from the SLC1 and SLC6 families seem to share their translocation mechanism with an increasing number of other SLC transporter families. Similarities and differences in structure, sequences and functional properties between transporters are an interesting source of information for structure function studies. 3D structures give a more precise idea on the architecture of these proteins and suggest specific role/s for individual amino acids. To associate the transporter structure with its function implies identifying suitable model systems and methods for investigating the time lapse of the transport event, characterizing their selectivity and quantifying their energy profile in biological membranes. The increasing availability of novel crystal structures, modern molecular modelling data, bioinformatics analysis, comparative and deep functional analysis in combination with the already available data are significantly accelerating the discovery of the key regions/amino acids in SLC transporters. This is leading to a better understanding of interaction with substrates, the action of inhibitors, the translocation steps, etc. which will help to fully comprehend the role of transporters in both physiological and pathological conditions and/or to develop new drugs.
Hundreds of transporters from different SLC subfamilies are expressed on the membranes of almost all living organisms, where they contribute to cell homeostasis by regulating the passage across the cells of neurotransmitters, nutrients, ions, etc. In current membrane transporters research, the study of the bacterial homologs strongly supports the advances in knowledge of the structural biology of the human transporters, and such distant ortholog proteins often result extremely important for e.g. the detailed understanding of a translocation mechanism. Studying closer orthologues of human SLC genes from less conventional (i.e. non-mammalian, non-bacterial) species together with comparing their sequences with the human members of the same family often represents a smart and low-cost alternative to identify amino acid residue(s) conserved in strategic positions during evolution. This helps in e.g. creating specific mutants of (a) human protein(s) to address their function by defining the role of single amino acids and/or functional regions. Conversely, small or large differences in aligned sequences can be correlated to significant differences in functionality, thus helping to increase our knowledge in transporter physiology, in drug interaction and in understanding the molecular basis of certain diseases and disorders.
The present collection is aimed to join contributions that discuss structure-function relationships in the SLC transporters with particular focus on substrate(s)-transporter(s) binding, inhibitor(s)-transporter(s) interactions, ion(s)-substrate(s) coupling, steps of the transport cycles, etc. The use of comparative approaches highlighting the function of transporters isolated from less conventional models such as lower vertebrates (amphibians, fishes, etc.), invertebrates (fruit flies, nematodes, etc.), lower metazoans (jellyfishes, etc.) and/or simple eukaryotes (yeasts, etc.) will be appreciated. A multidisciplinary approach that combines e.g. in silico modelling with structure-function in vitro and in vivo, finding the appropriate model for a transport system, could be a type of contribution to include in this present collection. We welcome submissions related to the following sub-topics:
• Structure-function relationships
• Mechanisms of transport
• Transport regulation in physiology and pathology
• Transporters: substrate, inhibitors and drug interaction
• Drug transport and transporters
• Experimental methods in SLC investigation
• Genomic research for new SLC transporters discovery
• Models of transport process
• Biophysical characterization of SLC proteins
• Bioinformatics and novel tools and methods to analyze SLC transporters
