Structural biology of solute carrier (SLC) membrane transport proteins

Figures & data

Figure 1. Representative available structures from different SLC families. Structures are downloaded from PDB (www.pdb.org) and presented using PyMOL (www.pymol.org). The helices were colored using rainbow from N to C terminal, with hues from blue through cyan closer to N terminal, while red through yellow closer to C terminal. Therefore, The TM regions are traceable in each structure by following the colors. Specifically, in MFS fold family members (e.g. LacY, GlpT, XylE, PepTso and EmrD), cool colors and warm colors are falls into two bundles, meaning that N and C terminal are separated into two bundles. This Figure is reproduced in color in Molecular Membrane Biology online.

Table 1. Solute carrier family and the corresponding folds: solute carrier family and the corresponding function, folds and human diseases.

Family	Function	Prokaryotic homolog structures	Eukaryotic (homolog) structures	Folds	Human diseases	References (diseases)
SLC1	Glutamate and neutral amino acid transport	GltPh, Pyrococcus horikoshii OT3; GltTk, Thermococcus kodakarensis KOD1	N/A	8 α-helical TMs (scaffolding and transport domain) and 2 hairpins (HP domain)	Huntington's disease, epilepsy, ischemia, Alzheimer's disease, Niemann-Pick disease, obsessive-compulsive disorder, Amyotrophic lateral sclerosis, Schizophrenia, Cerebellar ataxia type 7, Spinocerebellar ataxia type 5	(Kanai et al., 2013)
SLC2	Glucose or d-xylose/H^+ symoport; Glucose uniport	XylE, Escherichia coli K12; GlcP, Staphylococcus epidermidis ATCC 12228	GLUT1, Homo sapiens; GLUT3, Homo sapiens; GLUT5, Bos Taurus and Rattus norvegicus	MFS fold, amino-(TMs 1–6) and carboxy-(TMs 7–12) terminal bundles	Paroxysmal exertion-induced dyskinesia, dystonia-18, GLUT1 deficiency syndrome Fanconi-Bickel syndrome, type 2 diabetes, renal hypouricemia, arterial tortuosity syndrome	(Mueckler & Thorens, 2013)
SLC3	Heteromeric amino acid transport	N/A	N/A		Cystinuria, hypotonia-cystinuria syndrome (HCS), related; cancer	(Fotiadis et al., 2013)
SLC4	Bicarbonate transport	N/A	Band 3		Hemolytic anemia, distal renal tubular acidosis, severe proximal renal tubular acidosis, ocular abnormalities, short stature, blindness, auditory impairment	(Romero et al., 2013)
SLC5	Sodium glucose cotransport	vSGLT, Vibrio parahaemolyticus;	N/A	LeuT fold, core domain (TMs 1, 2, 6 and 7) and scaffold hash domain (TMs 3, 4, 8 and 9)	Glucose galactose malabsorption, OMIM 182380, familial renal glucosuria, OMIM 182381, Down’s syndrome, OMIM 600444, iodide transport defect (ITD) thyroid hormonogenesis, OMIM 601843	(Wright, 2013)
SLC6	Sodium- and chloride-dependent neurotransmitter transport	LeuT, Aquifex aeolicus VF; MhsT, Bacillus halodurans	DAT, Drosophila; SERT, Homo sapiens	LeuT fold	Epilepsy, schizophrenia, anxiety, ADHD, depression, orthostatic intolerance, anorexia nervosa, cardiovascular disorders, Parkinson disease, Tourette syndrome, addiction, major affective disorders, autism Gastrointestinal disorders, premature ejaculation, obesity, schizophrenia OCD, pain, spasticity, hyperekplexia, taurine deficiency diseases, retinal blindness, abnormal renal development, creatine deficiency syndrome, mental retardation, musculoskeletal disorders, cardiomyopathy, obesity, hyperglycinuria, Hartnup disorder, hypertension, iminoglycinuria	(Pramod et al., 2013)
SLC7	Cationic amino acid transport/glycoprotein-related	ApcT, Methanocaldococcus jannaschii	N/A	LeuT fold	Cancer, lysinuric protein intolerance (LPI), cystinuria, isolated cystinuria	(Fotiadis et al., 2013)
SLC8	Na^+/Ca^2+ exchange	YfkE, Bacillus subtilis subsp. subtilis str. 168; NCX_Mj, Methanocaldococcus jannaschii DSM 2661	VCX1, Saccharomyces cerevisiae S288c	CaCA folds^a, “5 + 5” inverted repeats, a tightly packed core (TMs 2–5 and 7–10) and loose TMs (TMs 1 and 6)	Heart disease such as ischemia and heart failure, primary pulmonary hypertension, Skeletal muscle dystrophy (possible)	(Khananshvili, 2013)
SLC9	Na^+/H^+ exchange	NhaA, Escherichia coli	N/A	Others antiparallel repeats: domain A (TMs 3,4,5, 10, 11 and 12) and domain B (TMs 2, 7, 8 in the center while TMs 1 and 6 are peripherally attached)	Congenital Na diarrhea, sudden infant death syndrome, X-linked mental retardation (Angelman syndrome, Christianson subtype), epilepsy, ataxia, familial autism, attention deficit, hyperactivity disorder, essential hypertension	(Donowitz et al., 2013)
SLC10	Sodium bile salt cotransport	ASBT, Neisseria meningitides; ASBT, Yersinia frederiksenii	N/A	Others antiparallel repeats: panel domain (TMs 1, 2, 6 and 7) and a core domain (TMs 3–5 and 8–10)	Primary bile acid malabsorption	(Claro da Silva et al., 2013)
SLC11	Proton-coupled metal ion transport	ScaDMT, Staphylococcus capitis	N/A	LeuT fold	Mycobacterium tuberculosis, Buruli ulcer, autoimmune disease, e.g. IDDM.; hypochromic microcytic anemia, Parkinson’s disease, esophageal, colorectal cancer	(Montalbetti et al., 2013)
SLC12	Electroneutral cation-coupled Cl^− cotransport	ApcT,Methanocaldococcus jannaschii	N/A	LeuT fold	Type I Bartter syndrome, Gitelman syndrome, ACCPN (Andermann syndrome)	(Arroyo et al., 2013)
SLC13	Human Na^+-sulfate/carboxylate cotransport	VcINDY, Vibrio cholera	N/A	TMs 2–6 and TMs 7–11 are inverted repeats with one helical hairpin HP domain each. TMs 4, 5, 9 and 10 are each broken into two segments.	Growth retardation, reduced fertility, seizures (KO mice), possible indirect role in glutaric aciduria type 1, Canavan disease	(Bergeron et al., 2013)
SLC14	Urea transport		UT-B, Bos Taurus	Channel like	N/A
SLC15	Proton oligopeptide cotransport	PepTSt, Streptococcus thermophilus LMG 18311; POT, Geobacillus kaustophilus; PepTSo, Shewanella oneidensis MR-1; YbgH, Escherichia coli	NRT1.1, Arabidopsis thaliana	MFS fold	Inflammatory bowel disease (colonic upregulation), lead exposure (2 haplotype associated with higher blood lead burden in male children^a)	(Smith et al., 2013)
SLC16	Monocarboxylate transport	N/A	N/A		Exercise-induced hyperinsulin-aemia hypo-glycaemia, Allan-Herndon-Dudley syndrome, juvenile cataracts with microcornea and renal glucosuria	(Halestrap, 2013)
SLC17	Vesicular glutamate transport	N/A	N/A		Gout, sialic acid storage disease (Salla disease), autosomal dominant non-syndromic deafness (DFNA25)	(Reimer, 2013)
SLC18	Vesicular amine transport	EmrD, Escherichia coli	N/A	MFS fold	Not known/Not clear
SLC19	Folate/thiamine transport	N/A	N/A		Methotrexate resistance, TRMA-thiamine-responsive megaloblastic anemia syndrome, biotin-responsive basal ganglia disease, Wernicke's-like encephalopathy	(Zhao & Goldman, 2013)
SLC20	Type III Na^+-phosphate cotransport	N/A	N/A		Idiopathic basal ganglia calcification (genetic defect)	(Forster et al., 2013)
SLC21	Organic anion transport	N/A	N/A		Statin-induced myopathy, Rotor syndrome, unconjugated hyperbilirubinemia, Rotor syndrome	(Hagenbuch & Stieger, 2013)
SLC22	Organic cation/anion/zwitterion transport	UraA, Escherichia coli	PiPT, Piriformospora indic	MFS fold (PipT); Others antiparallel repeats: “7 + 7” inverted repeats (UraA), core domain (TMs 1–4 and 8–11) and gate domain (TMs 5–7 and 12–14).	Cytotoxicity of cisplatin, oxaliplatin and picoplatin, Prostate cancer, coronary heart disease, obsessive compulsive disorder, Rheumatoid arthritis, Crohn’s disease, Primary systemic carnitine deficiency, Reduced plasma uric acid level, renal hypo-uricemia, gout, cyclosporine-A induced hyperuricemia, bipolar l disorder	(Koepsell, 2013)
SLC23	Na^+-dependent ascorbic acid transport	N/A	N/A		Found to be associated with spontaneous preterm delivery; gastric cancer; risk for lymphoma; head and neck squamous cell carcinomas (HNSCC); Cardiovascular disease	(Burzle et al., 2013)
SLC24	Na^+/(Ca^2+–K^+) exchange	N/A	N/A		Congenital stationary night blindness	(Schnetkamp, 2013)
SLC25	Mitochondrial carrier	N/A	Aac2p, Saccharomyces cerevisiae;Aac3p, Saccharomyces cerevisiae; ANT1, Bos Taurus	Three α-helical stretches connecting the six odd- and even-numbered helices	Mitochondrial phosphate carrier deficiency, AAC1 deficiency, autosomal dominant progressive external ophthalmoplegia (adPEO), Obesity, type 2 diabetes, congenital hyperinsulinism, autism, citrullinemia type II (CTLN2), neonatal intrahepatic cholestasis (NICCD), hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome, congenital Amish microcephaly (MCPHA), neuropathy with bilateral striatal necrosis, carnitine acylcarnitine carrier deficiency, early epileptic encephalopathy, sperato-genesis, sideroblastic anemia	(Palmieri, 2013)
SLC26	Multifunctional anion exchange	SLC26Dg, Deinococcus geothermalis	N/A	Others with “Inverted Repeat”	Oxalate urolithiasis, nephrocalcinosis, urinary sulfate wasting, hepatotoxicity, diastrophic dysplasia, broad bone-, platyspondylic variant, atelosteogenesis II, achondrogenesis IB, multiple epiphyseal, dysplasia type 4, De la Chapelle dysplasia, congenital chloride diarrhea, Pendred syndrome, deafness (DFNB4), enlargement of the vestibular acqueduct, grossly normal: loss or reduction of cAMP-stimulated HCO3^- secretion in GI epithelia, gastric hypochlorhydria, distal renal tubular acidosis, male infertility	(Alper & Sharma, 2013)
SLC27	Fatty acid transport	N/A	N/A		Restrictive dermopathy (OMIM #275210)	(Anderson & Stahl, 2013)
SLC28	Na^+-coupled nucleoside transport	vcCNT, Vibrio cholerae	N/A	Similar to Glutamate transporter Gltph	N/A
SLC29	Facilitative nucleoside transport	N/A	N/A		H syndrome (hepatosplenomegaly, hearing loss, hyperpigmentation, hypertrichosis, hypogonadism, low height, heart anomalies and hyperglycemia mellitus), pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome (PHID), Faisalabad histiocytosis syndrome (FHC) and Rosai-Dorfman disease (RDD)	(Young et al., 2013)
SLC30	Zinc efflux	YiiP, Escherichia coli; YiiP, Shewanella oneidensis MR-1	N/A	Six TMs and one hydrophilic CTD domain (C-terminal domain)	Embryonic lethala, reduced zinc content in nursing women, seizures, learning deficit, memory loss lethal milk, bone abnormalities, heart failure, Alzheimer, prostate cancer, low adiposity, diet-induced diabetes diabetes	(Huang & Tepaamorndech, 2013)
SLC31	Copper transport	N/A	N/A		Maybe involved in degenerative neuronal diseases, cardiovascular disease and intrinsic and acquired resistance to platinum-based chemotherapeutics	(Kim et al., 2013)
SLC32	Vesicular inhibitory amino acid transport	N/A	N/A		N/A
SLC33	Acetyl-CoA transport	N/A	N/A		Autosomal dominant spastic paraplegia (SPG42)	(Hirabayashi et al., 2013)
SLC34	Type II Na^+-phosphate cotransport	N/A	N/A		G/XLH, G/ADHR, A/OHO, nephrocalciosis, hypo-phosphatemia, urolithiasis, osteoporosis, pulmonary alveolar microlithiasis, testicular microlithiasis, hypophosphatemic rickets with hypercalciuria	(Forster et al., 2013)
SLC35	Nucleoside-sugar transport	N/A	N/A		Congenital disorder of glycosylation IIf, congenital disorder of glycosylation IIc, Schneckenbecken dysplasia	(Song, 2013)
SLC36	Proton-coupled amino acid transport	ApcT, Methanocaldococcus jannaschii	N/A	LeuT fold	Mutations of PAT2: hyperglycinurea and iminoglycinurea	(Schioth et al., 2013)
SLC37	Sugar-phosphate/phosphate exchange	GlpT, Escherichia coli; LacY, Escherichia coli	N/A	MFS fold	GSD-Ib/GSD-Ic, (OMIM232220/232240)	(Chou et al., 2013)
SLC38	System A and System N sodium-coupled neutral amino acid transport	N/A	N/A		SLC38A2 is activated in prostate cancer; SLC38A3 mRNA is upregulated in human gliomas	(Schioth et al., 2013)
SLC39	Metal ion transport	BbFPN, Bdellovibrio bacteriovorus	N/A	MFS fold	Prostate cancer, neurodegeneration, AE, pancreatic cancer, liver cancer, cervicale, neuroblastoma, breast cancer, inflammation, SCD-EDS, asthma, inflammation, colorectal cancer	(Jeong & Eide, 2013)
SLC40	Basolateral iron transport	N/A	N/A		Hemochromatosis type 4, breast cancer	(Montalbetti et al., 2013)
SLC41	MgtE-like magnesium transport	N/A	N/A		Mutations in PARK16 locus	(Sahni & Scharenberg, 2013)
SLC42	Rh ammonium transport	AmtB, Escherichia coli; Rh50, Nitrosomonas europaea; Amt-1, Archaeoglobus fulgidus	RhCG, homo sapiens	Channel	Rhnull-regulator, Rhmod, OHSt, renal distal, tubular acidosis	(Nakhoul & Lee Hamm, 2013)
SLC43	Na^+-independent, system-L-like amino acid transport	N/A	N/A		Androgen-dependent cancers	(Bodoy et al., 2013)
SLC44	Choline-like transport	N/A	N/A		Neonatal respiratory distress syndrome, auto-immune hearing loss, transfusion-related acute lung injury	(Traiffort et al., 2013)
SLC45	H^+/sugar cotransport	N/A	N/A		Hypercapnia, OCA4, skin/hair/eye pigmentation, melanoma, prostate cancer, Huntington disease	(Vitavska & Wieczorek, 2013)
SLC46	Folate transport	N/A	N/A		Hereditary folate malabsorption	(Zhao & Goldman, 2013)
SLC47	Multidrug and Toxin Extrusion (MATE)	N/A	N/A		Maybe involved in metformin-induced lactic acidosis	(Motohashi & Inui, 2013)
SLC48	Heme transport	N/A	N/A		N/A
SLC49	FLVCR-related transport	N/A	N/A		Posterior column ataxia, retinitis pigmentosa (PCARP) syndrome, Diamond-Blackfan anemia (DBA), Fowler syndrome, ovarian cancer, renal cell, prostate cancers	(Khan & Quigley, 2013)
SLC50	Sugar efflux	N/A	N/A		N/A
SLC51	Steroid-derived molecules transport	N/A	N/A		Elevated levels of SLC51A and SLC51B mRNA and protein are found in primary biliary cirrhosis	(Ballatori et al., 2013)
SLC52	Riboflavin transport	N/A	N/A		Haploinsufficiency of SLC52A1 could cause mild riboflavin deficiency; Brown-Vialetto-Van Laere syndrome	(Yonezawa & Inui, 2013)
SLC53	Phosphate carriers	N/A	N/A		Primari familial brain calcification (PFBC); renal phenotype; neurological disorders	(Ansermet et al., 2017; Legati et al., 2015; Moura & Oliveira, 2015)
SLC54	Mitochondrial pyruvate carriers	N/A	N/A		N/A
SLC55	Mitochondrial cation/proton exchangers	N/A	N/A		Wolf–Hirschhorn syndrome; Biomarker for breast and liver cancer	(Endele et al., 1999; Ko et al., 2003)
SLC56	Sideroflexins				Mostly adult kidney and liver (mouse)	(Fleming et al., 2001)
SLC57	NiPA-like magnesium transporter	N/A	N/A		Dominant hereditary spastic paraplegia (SPG6), amyotrophic lateral sclerosis (ALS); Congenital ichthyosis	(Blauw et al., 2012; Dahlqvist et al., 2007; Lefevre et al., 2004; Rainier et al., 2003)
SLC58	MagT-like magnesium transporter	N/A	N/A		“XMEN syndrome”	(Li et al., 2011)
SLC59	Sodium-dependent lysophosphatidylcholine symporter	N/A	N/A		Progressive microcephaly syndrome; Physiologically, might play a role in blood-brain barrier (BBB) drug delivery and is the syncytin-2 receptor	(Alakbarzade et al., 2015; Ben-Zvi et al., 2014; Toufaily et al., 2013; Wang et al., 2016)
SLC60	Glucose transporter	N/A	N/A		Tumor suppressor and biomarker for hepatic metastasis in gastric cancer	(Kanda et al., 2016)
SLC61	Molybdate transporter	N/A	N/A		Tumor suppressor and biomarker for hepatic metastasis in gastric cancer.	(Kanda et al., 2016)
SLC62	Pyrophosphate transporter	N/A	N/A		Craniometaphyseal dysplasia, familial calcium pyrophosphate dihydrate deposition disease (chondrocalcinosis), ankylosing spondylitis	(Nurnberg et al., 2001; Reichenberger et al., 2001; Tsui et al., 2005; Williams et al., 2002)
SLC63	Sphingosine-phosphate transporter	N/A	N/A		N/A
SLC64	Golgi Ca^2+/H^+ exchanger	N/A	N/A		Congenital disorder of glycosylation (CDG) type II	(Foulquier et al., 2012; Zeevaert et al., 2013)
SLC65	NPC-type cholesterol transporter	N/A	N/A		Niemann–Pick disease type C	(Carstea et al., 1993)

The prokaryotic homolog members are classified into the corresponding human SLCs mainly based on TCDB database (transporter classification database), the bioparadigms (http://www.bioparadigms.org/slc/intro.htm) and the mpstruc database (http://blanco.biomol.uci.edu/mpstruc/). Functions are based on http://slc.bioparadigms.org/.

^a Means only one example of the family protein is shown. The TM numbers may vary in different members within the same family.

Most of the non-human structure available SLCs were classified into the corresponding human SLC families based on the exist information about SLCs on TCDB database (transporter classification database) which details a comprehensive IUBMB approved classification system for membrane transport proteins, the Bioparadigms (http://www.bioparadigms.org/slc/intro.htm) which specially presents the latest information about SLC proteins and the mpstruc database (http://blanco.biomol.uci.edu/mpstruc/).

Table 2. Solute carrier family and the corresponding folds: categories of SLC structures based on folds.

Folds	SLC family	Species	Protein	Function
MFS fold	SLC2	Escherichia coli	XylE	d-xylose/H^+ symoport
		Staphylococcus epidermidis	GlcP	Glucose/H^+ symport
		Homo sapiens	GLUT1	Glucose transport (uniporter)
		Homo sapiens	GLUT3	Glucose transport (uniporter)
		Bos Taurus and Rattus norvegicus	GLUT5	Glucose transport (uniporter)
	SLC15	Streptococcus thermophilus LMG	PepTSt	Di-or tripeptide/H^+ symport
		Geobacillus kaustophilus	POT	Peptide/H^+ symport
		Shewanella oneidensis MR-1	PepTSo	Oligopeptide/H^+ symport
		Escherichia coli	YbgH	Oligopeptide/H^+ symport
		Arabidopsis thaliana	NRT1.1	Nitrate/H^+ symport
	SLC18	Escherichia coli	EmrD	Multidrug transport/H^+ symport
	SLC22	Piriformospora indic	PiPT	Phosphate/H^+ symoport
	SLC37	Escherichia coli	GlpT	Glycerol-3-phosphate/inorganic phosphate antiport
		Escherichia coli	LacY	Beta-galactosides/H^+ symport
	SLC39	Bdellovibrio bacteriovorus	BbFPN	Metal ion transport
LeuT fold	SLC5	Vibrio parahaemolyticus	vSGLT	Galactose/Na^+ symport
	SLC6	Aquifex aeolicus VF	LeuT	Neurotransmitter/Na^+ symport
		Bacillus halodurans	MhsT	Neurotransmitter/Na^+ symport
		Drosophila	DAT	Dopamine transport/Na^+ symport
		Homo sapiens	SERT	serotonin/Na^+ symport
	SLC7/12/36	Methanocaldococcus jannaschii	ApcT	Amino acid/H^+ symport
	SLC11	Staphylococcus capitis	ScaDMT	Divalent metal cation/H^+ symport
Other antiparallel folds	SLC4	Homo sapiens	Band 3	Cl^−/HCO3^− exchange
	SLC9	Escherichia coli	NhaA	Na^+/H^+ antiporter
	SLC10	Yersinia frederiksenii/Neisseria meningitidis	ASBT	Bile acid/Na^+ symport
	SLC22	Escherichia coli	UraA	Uracil/H^+ symport
	SLC26	Deinococcus geothermalis	SLC26Dg	Fumarate/H^+ symport
Others
with”HP domains”	SLC1	Pyrococcus horikoshii	Gltph	Glutamate transport
		Thermococcus kodakarensis	GltTk	Glutamate transport
	SLC13	Vibrio cholera	vcINDY	Human Na^+-sulfate/carboxylate cotransport
	SLC28	Vibrio cholera	vcCNT	Na^+-coupled nucleoside transport
Mitochondrial Carriers (6TMs with 3 similar repeats)	SLC25	Saccharomyces cerevisiae	Aac2p	Cytoplasmic ADP/mitochondrial ATP exchange
		Saccharomyces cerevisiae	Aac3p	Cytoplasmic ADP/mitochondrial ATP exchange
		Bos Taurus	ANT1	Cytoplasmic ADP/mitochondrial ATP exchange
Zinc transporters (“V” shaped homodimer with a CTD)	SLC30	Escherichia coli	YiiP	Zinc efflux
		Shewanella oneidensis MR-1	YiiP	Zinc efflux
CaCA folds	SLC8	Bacillus subtilis subsp. subtilis	YfkE	Na^+/Ca^2+ exchange
		Methanocaldococcus jannaschii	NCX_Mj	Na^+/Ca^2+ exchange
		Saccharomyces cerevisiae	VCX1	Na^+/Ca^2+ exchange
Channel like Transporters	SLC14	Bos Taurus	UT-B	Urea transport
	SLC42	Escherichia coli	AmtB	Rh ammonium transport
		Archaeoglobus fulgidus	Amt-1	Rh ammonium transport
		Nitrosomonas europaea	Rh50	Rh ammonium transport
		Homo sapiens	RhCG	Rh ammonium transport

Most of the non-human structure available SLCs were classified into the corresponding human SLC families based on the exist information about SLCs on TCDB database (transporter classification database) which details a comprehensive IUBMB approved classification system for membrane transport proteins, the Bioparadigms (http://www.bioparadigms.org/slc/intro.htm) which specially presents the latest information about SLC proteins, and the mpstruc database (http://blanco.biomol.uci.edu/mpstruc/).

Figure 2. Left, topology diagrams of MFS fold representative protein PepTso and LeuT fold protein LeuT. Right, structures are shown as cartoon using PyMOL (www.pymol.org). This Figure is reproduced in color in Molecular Membrane Biology online.

Figure 3. (A) Symport model of MFSs fold SLC proteins based on structures from sugar transporters (LacY, XylE), POT family proteins (POT, PepTst, PepTso, YbgH), NRT1.1, EmrD and PipT. Specifically, sequential release in PipT seems different from the other transporters by releasing the proton first, followed by exist of substrate. C: conformation. Cout: outward conformation. Cin: inward conformation. Cin-occluded: Occluded conformation. Protein structures captured in corresponding conformations were colored blue. (B) Antiport model of MFSs fold SLC proteins based on structures from GlpT. (C) Symport model of LeuT fold SLC proteins based on structures from LeuT, DAT, MhsT, ApcT and vSGLT. This Figure is reproduced in color in Molecular Membrane Biology online.

Figure 4. (A) Close-up view of the substrate/ion binding sites. Substrate binding sites of PepTso, PipT, XylE and LeuT and Na site of vSGLT were shown using Pymol. Bonds between atoms were not shown for clarity. For PepTso, since the presence of substrate is based on predictions from literature and map density, real substrate was not able to be shown here. (B) Top, Na2 site of LeuT. Distance between Na2 and Na1 (Leu substrate) were shown. Bottom, extracellular gate of LeuT. This Figure is reproduced in color in Molecular Membrane Biology online.

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