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Membrane Proteins

SLC proteins

  • NKCC1, S12A2

    3.2 Å
    38562
    P55011

  • EAAT3, SLC1A1

    2.9 Å
    37796
    P43005

  • ZnT8 (D110N, D224N), SLC30A8

    3.4 Å
    37816
    Q8IWU4

Solute carriers (SLCs) are a group of membrane transport proteins, comprising over 400 members classified into 66 families 【1-2】. SLCs are widely distributed within cells, located not only on the plasma membrane but also on the membranes of organelles such as the nuclear membrane, endoplasmic reticulum, and mitochondria 【3-4】. SLC family proteins facilitate the transmembrane transport of numerous nutrients and metabolites, including metal ions, inorganic ions, organic ions, amino acids, lipids, sugars, neurotransmitters, nucleic acids, and pharmaceutical drugs 【5-7】.

Studies have shown that abnormal expression or functional deficiencies of SLC proteins are closely associated with the pathogenesis and development of various diseases, including tumors, metabolic diseases, cardiovascular diseases, and immune system and neurological dysfunctions. Consequently, functional research on this protein family has garnered significant attention in recent years 【6】.

Particularly in tumors, members of the SLC family serve as the main component of amino acid transporters. The high uptake of amino acids by tumor cells is primarily achieved through the overexpression of various amino acid transporters 【6-7】. Therefore, targeting amino acid transporters within the SLC family to suppress tumor growth represents an effective therapeutic strategy.

References

【1】 Hediger M A, Romero M F, Peng J B, et al. The ABCs of solute carriers: physiological, pathological and therapeutic implications of human membrane transport proteins: Introduction[J]. Pflügers Archiv, 2004, 447: 465-468.
【2】 Perland E, Fredriksson R. Classification systems of secondary active transporters[J]. Trends in pharmacological sciences, 2017, 38(3): 305-315.
【3】 Ben Mariem O, Di Domizio A, Palazzolo L, et al. Deciphering the ligand/xenobiotic molecular recognition mechanism in SLC transporters via a new structural binding site analysis[J]. 2021.
【4】 Li Q, Zhou T, Wu F, et al. Subcellular drug distribution: mechanisms and roles in drug efficacy, toxicity, resistance, and targeted delivery[J]. Drug Metabolism Reviews, 2018, 50(4): 430-447.
【5】 Liu X. Transporter-mediated drug-drug interactions and their significance[J]. Drug Transporters in Drug Disposition, Effects and Toxicity, 2019: 241-291.
【6】 Zhou S, Shu Y. Transcriptional regulation of solute carrier drug transporters[J]. Drug Metabolism and Disposition, 2022, 50(9): 1238-1250.
【7】 Cesar-Razquin A, Snijder B, Frappier-Brinton T, et al. A call for systematic research on solute carriers[J]. Cell, 2015, 162(3): 478-487.

Single Particle Analysis (SPA)

Cryo-EM Structure Gallery

Single Particle Analysis