Leave a Message
My Cart ()
Inquiry Basket
Contact Us

Structural Research of Solute Carrier (SLC) Transporter Superfamily

Inquiry

The solute carrier (SLC) superfamily currently includes 458 transport proteins from 65 families that carry a wide range of substances across cell membranes. Human SLCs transport nutrients, metabolites, exogenous substances, and drugs, including inorganic ions, amino acids, sugars, neurotransmitters, lipids, and drugs. Most SLCs function as coupled co-transporter proteins that utilize the H+ or Na+ gradient as a driving force for the transport of substrates against the concentration gradient into the cell, and play essential roles in various physiological and pharmacological processes.

SLC's function in health and disease

As one of the major regulators of cellular substance transport, SLC proteins are associated with a wide range of cellular and physiological processes. Some SLC proteins are tissue-specific, such as the SLC6 and SLC18 family members, which regulate the concentration of neurotransmitters in synapses. Many SLCs are also involved in the transport of essential nutrients across selective barriers between tissues, such as the blood-brain barrier or intestinal epithelium. Some SLCs act as "receptors" and participate in intracellular signaling systems. For example, SLC30A8, a zinc transporter protein closely related to diabetes, is highly expressed in pancreatic cell membranes. In addition, some SLC proteins contain viral binding sites that facilitate viral entry into the cell.

Advances in structural research of the SLC family

SLC proteins contain between 1 and 16 transmembrane (TM) domains, although most tend to contain 7 and 12 TM domains. However, most SLC transporter proteins share some common structural features, namely the pseudo-symmetry of the core TM domains. The two most common structural folds in SLC proteins are the major facilitator superfamily (MFS) and the leucine transporter protein (LeuT)-like folds. The MFS fold consists of a pseudo-repeat of two six TM helices linked by a cytoplasmic loop, and the LeuT fold consists of two 5-TM helices, each containing a bundle and a scaffolding domain. The MFS fold consists of two pseudo repeats of 6-TM helices connected by a cytoplasmic loop, and the LeuT fold consists of two 5-TM helices, each containing a bundle and a scaffold domain.

Folds of SLC14A2, SLC31, and SLC30A5. Figure 1. Folds of SLC14A2, SLC31, and SLC30A5. (Xie T, et al., 2022)

Protein Organism Method Resolution PDB Entry ID
Choline transporter-like protein 1 Homo sapiens Cryo-EM single particle analysis 3.86 Å 7WWB
LaINDY crystallized in the presence of alpha-ketoglutarate and malate Lactobacillus acidophilus X-ray diffraction 2.86 Å 6WTW
LaINDY-alpha-ketoglutarate complex Lactobacillus acidophilus Cryo-EM single particle analysis 3.71 Å 6WU4
VcINDY-Na+ in amphipol Vibrio cholerae Cryo-EM single particle analysis 3.16 Å 6WU3
LaINDY-malate complex Lactobacillus acidophilus Cryo-EM single particle analysis 3.36 Å 6WU2
Apo LaINDY Lactobacillus acidophilus Cryo-EM single particle analysis 3.09 Å 6WU1
Inhibited I (Chloride + Salicylate) Tursiops truncatus Cryo-EM single particle analysis 3.8 Å 7S9A
Inhibited II (Sulfate +Salicylate) state Tursiops truncatus Cryo-EM single particle analysis 3.7 Å 3S9E
Sensor Up (compact) state Tursiops truncatus Cryo-EM single particle analysis 3.3 Å 7S8X
Sensor Down I (Expanded) state Tursiops truncatus Cryo-EM single particle analysis 4.2 Å 7S9B
Sensor Down II (Expanded II) state Tursiops truncatus Cryo-EM single particle analysis 6.7 Å 7S9C
Intermediate state Tursiops truncatus Cryo-EM single particle analysis 4.6 Å 7S9D
VcINDY in complex with terephthalate Vibrio cholerae X-ray diffraction 3.92 Å 6WTX
A bacterial cationic amino acid transporter (CAT) homologue bound to Arginine. Escherichia coli K-12 X-ray diffraction 3.13 Å 6F34
VcINDY-Na-Fab84 in nanodisc Homo sapiens Cryo-EM single particle analysis 3.15 Å 6WW5
The sodium-dependent phosphate transporter Thermotoga maritima MSB8 X-ray diffraction 2.302 Å 6L85
HsPepT1 bound to Ala-Phe in the outward-facing occluded conformation Homo sapiens Cryo-EM single particle analysis 4.1 Å 7PMW
HsPepT1 bound to Ala-Phe in the outward-facing open conformation Homo sapiens Cryo-EM single particle analysis 3.5 Å 7PMX
Apo HsPepT1 in the outward facing open conformation Homo sapiens Cryo-EM single particle analysis 3.9 Å 7PN1
murine Solute Carrier 26 family member A9 (Slc26a9) anion transporter in an intermediate state Mus musculus Cryo-EM single particle analysis 7.77 Å 6RTF
Proton symporter in the inward open form Escherichia coli X-ray diffraction 2.915 Å 6E9N
Proton symporter mutant E133Q in the outward substrate-bound form Escherichia coli X-ray diffraction 3.501 Å 6E9O
Peptide transporter DtpA-nanobody in complex with valganciclovir Escherichia coli X-ray diffraction 2.645 Å 6GS4
Divalent anion/Na+ symporter and a humanized variant Vibrio cholerae O1 biovar El Tor str. N16961 X-ray diffraction 2.8 Å 5UL7
Solute Carrier 26 family member A9 (Slc26a9) anion transporter in the inward-facing state Mus musculus Cryo-EM single particle analysis 3.96 Å 6RTC
SLC4 transporter Bor1p in an inward-facing conformation Saccharomyces mikatae X-ray diffraction 5.9 Å 5SV9
OATP1B1 Homo sapiens Cryo-EM single particle analysis 3.6 Å 8PHW
Proton-coupled folate transporter at pH 6.0 bound to pemetrexed Gallus gallus Cryo-EM single particle analysis 3.3 Å 7BC7
Concentrative nucleoside transporter CNT3 Homo sapiens Cryo-EM single particle analysis 3.6 Å 6KSW
b(0,+)AT1 Homo sapiens Cryo-EM single particle analysis 3.4 Å 6YV1
Sulfate transporter AtSULTR4;1 Arabidopsis thaliana Cryo-EM single particle analysis 2.75 Å 7LHV
A bacterial dicarboxylate/sodium symporter Vibrio cholerae X-ray diffraction 3.196 Å 4F35
SLC26A9 Homo sapiens Cryo-EM single particle analysis 2.6 Å 7CH1
Peptide transporter PepT2 Lama glama Cryo-EM single particle analysis 3.5 Å 7NQK

Table 1. Structural research of the solute carrier (SLC) transporter superfamily.

Structural analysis of the solute carrier (SLC) transporter superfamily is essential for revealing the regulatory mechanisms of multiple physiological processes. Structural research can help to understand the functional mechanism of SLC in disease formation, signaling pathways, and interactions with other proteins. It provides strategies for developing new attractive drug targets.

Creative Biostructure is a leading biotech company focused on protein structural biology. We provide SLC and various kinds of services related to protein structure research, such as X-ray crystallography, cryo-electron microscopy (cryo-EM), and nuclear magnetic resonance (NMR) services. Our professionals have extensive experience and cutting-edge equipment to provide comprehensive support for your research. If you are interested in protein structure analysis and related areas, please feel free to contact us for more details.

References

  1. Xie T, et al. Rational exploration of fold atlas for human solute carrier proteins. Structure. 2022. 30(9): 1321-1330. e5.
  2. Pizzagalli MD, et al. A guide to plasma membrane solute carrier proteins. FEBS J. 2021. 288(9): 2784-2835.
  3. Bai X, et al. Structural biology of solute carrier (SLC) membrane transport proteins. Mol Membr Biol. 2017. 34(1-2): 1-32.
  4. Ferrada E, Superti-Furga G. A structure and evolutionary-based classification of solute carriers. iScience. 2022. 25(10): 105096.
OUR VALUED PARTNERSHIPS
mit harvard stanford nih abbvie novartis amgen gsk regeneron sanofi

Online Inquiry

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Inquiry
back to top
Advertisement Learn More