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Structure and Function of SLC4 Family [Formula: see text] Transporters.

Liu Y, Yang J, Chen LM - Front Physiol (2015)

Bottom Line: Dysfunctions of these transporters are associated with a series of human diseases.Based upon the proposed topology models, mutational and functional studies have identified important structural elements likely involved in the ion translocation by the SLC4 transporters.In the present article, we review the advances during the past decades in understanding the structure and function of the SLC4 transporters.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, Department of Biophysics and Molecular Physiology, School of Life Science and Technology, Huazhong University of Science and Technology Wuhan, China.

ABSTRACT
The solute carrier SLC4 family consists of 10 members, nine of which are [Formula: see text] transporters, including three Na(+)-independent Cl(-)/[Formula: see text] exchangers AE1, AE2, and AE3, five Na(+)-coupled [Formula: see text] transporters NBCe1, NBCe2, NBCn1, NBCn2, and NDCBE, as well as "AE4" whose Na(+)-dependence remains controversial. The SLC4 [Formula: see text] transporters play critical roles in pH regulation and transepithelial movement of electrolytes with a broad range of demonstrated physiological relevances. Dysfunctions of these transporters are associated with a series of human diseases. During the past decades, tremendous amount of effort has been undertaken to investigate the topological organization of the SLC4 transporters in the plasma membrane. Based upon the proposed topology models, mutational and functional studies have identified important structural elements likely involved in the ion translocation by the SLC4 transporters. In the present article, we review the advances during the past decades in understanding the structure and function of the SLC4 transporters.

No MeSH data available.


Related in: MedlinePlus

Putative models of topological organization of SLC4 transporters (A,B) and 3D crystal structure of Nt domain of AE1 (C). For the convenience to compare the sequence assignments, both topological models A and B use human NBCe1-A for illustration. The numbers (according to accession #AAC51645.1) at both ends of each putative TM indicate the proposed initial and last residues of the TM in each model. Experimentally, model A is largely based on the studies with AE1 by N-glycosylation scanning mutagenesis (Popov et al., 1997, 1999) and cysteine scanning mutagenesis (Tang et al., 1998; Zhu et al., 2003). The front half of TMD (TM1-TM9) of model B is basically consistent with model A except for some minor deviations in the boundaries of TMs. The assignment of the Ct half from EL5-TM14 in model B is based upon the cysteine-scanning mutagenesis study on NBCe1 (Zhu et al., 2010a,b) and the structural modelings with AE1 (Barneaud-Rocca et al., 2013; Bonar et al., 2013). Panel C shows the 3D structure of the dimer of the Nt domain of human AE1. The model was created based on the crystal structure of the Nt of human AE1 (PDB ID #4KY9) using Protein Workshop 4.2.0 from RCSB Protein Data Bank (Moreland et al., 2005). The hydrophobicity surface (blue least, red most) was generated by using a Euclidean Distance Transform (Xu and Zhang, 2009).
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Figure 2: Putative models of topological organization of SLC4 transporters (A,B) and 3D crystal structure of Nt domain of AE1 (C). For the convenience to compare the sequence assignments, both topological models A and B use human NBCe1-A for illustration. The numbers (according to accession #AAC51645.1) at both ends of each putative TM indicate the proposed initial and last residues of the TM in each model. Experimentally, model A is largely based on the studies with AE1 by N-glycosylation scanning mutagenesis (Popov et al., 1997, 1999) and cysteine scanning mutagenesis (Tang et al., 1998; Zhu et al., 2003). The front half of TMD (TM1-TM9) of model B is basically consistent with model A except for some minor deviations in the boundaries of TMs. The assignment of the Ct half from EL5-TM14 in model B is based upon the cysteine-scanning mutagenesis study on NBCe1 (Zhu et al., 2010a,b) and the structural modelings with AE1 (Barneaud-Rocca et al., 2013; Bonar et al., 2013). Panel C shows the 3D structure of the dimer of the Nt domain of human AE1. The model was created based on the crystal structure of the Nt of human AE1 (PDB ID #4KY9) using Protein Workshop 4.2.0 from RCSB Protein Data Bank (Moreland et al., 2005). The hydrophobicity surface (blue least, red most) was generated by using a Euclidean Distance Transform (Xu and Zhang, 2009).

Mentions: As shown in Figure 2, the entire polypeptides of the SLC4 transporters contain three major domains: (1) a large intracellular amino-terminal (Nt) domain varying from ~300 to 700 aa in length; (2) a multiple-spanning transmembrane domain (TMD) of ~500 aa in length; (3) a small intracellular carboxyl-terminal (Ct) domain of ~40-130 aa in length.


Structure and Function of SLC4 Family [Formula: see text] Transporters.

Liu Y, Yang J, Chen LM - Front Physiol (2015)

Putative models of topological organization of SLC4 transporters (A,B) and 3D crystal structure of Nt domain of AE1 (C). For the convenience to compare the sequence assignments, both topological models A and B use human NBCe1-A for illustration. The numbers (according to accession #AAC51645.1) at both ends of each putative TM indicate the proposed initial and last residues of the TM in each model. Experimentally, model A is largely based on the studies with AE1 by N-glycosylation scanning mutagenesis (Popov et al., 1997, 1999) and cysteine scanning mutagenesis (Tang et al., 1998; Zhu et al., 2003). The front half of TMD (TM1-TM9) of model B is basically consistent with model A except for some minor deviations in the boundaries of TMs. The assignment of the Ct half from EL5-TM14 in model B is based upon the cysteine-scanning mutagenesis study on NBCe1 (Zhu et al., 2010a,b) and the structural modelings with AE1 (Barneaud-Rocca et al., 2013; Bonar et al., 2013). Panel C shows the 3D structure of the dimer of the Nt domain of human AE1. The model was created based on the crystal structure of the Nt of human AE1 (PDB ID #4KY9) using Protein Workshop 4.2.0 from RCSB Protein Data Bank (Moreland et al., 2005). The hydrophobicity surface (blue least, red most) was generated by using a Euclidean Distance Transform (Xu and Zhang, 2009).
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Related In: Results  -  Collection

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Figure 2: Putative models of topological organization of SLC4 transporters (A,B) and 3D crystal structure of Nt domain of AE1 (C). For the convenience to compare the sequence assignments, both topological models A and B use human NBCe1-A for illustration. The numbers (according to accession #AAC51645.1) at both ends of each putative TM indicate the proposed initial and last residues of the TM in each model. Experimentally, model A is largely based on the studies with AE1 by N-glycosylation scanning mutagenesis (Popov et al., 1997, 1999) and cysteine scanning mutagenesis (Tang et al., 1998; Zhu et al., 2003). The front half of TMD (TM1-TM9) of model B is basically consistent with model A except for some minor deviations in the boundaries of TMs. The assignment of the Ct half from EL5-TM14 in model B is based upon the cysteine-scanning mutagenesis study on NBCe1 (Zhu et al., 2010a,b) and the structural modelings with AE1 (Barneaud-Rocca et al., 2013; Bonar et al., 2013). Panel C shows the 3D structure of the dimer of the Nt domain of human AE1. The model was created based on the crystal structure of the Nt of human AE1 (PDB ID #4KY9) using Protein Workshop 4.2.0 from RCSB Protein Data Bank (Moreland et al., 2005). The hydrophobicity surface (blue least, red most) was generated by using a Euclidean Distance Transform (Xu and Zhang, 2009).
Mentions: As shown in Figure 2, the entire polypeptides of the SLC4 transporters contain three major domains: (1) a large intracellular amino-terminal (Nt) domain varying from ~300 to 700 aa in length; (2) a multiple-spanning transmembrane domain (TMD) of ~500 aa in length; (3) a small intracellular carboxyl-terminal (Ct) domain of ~40-130 aa in length.

Bottom Line: Dysfunctions of these transporters are associated with a series of human diseases.Based upon the proposed topology models, mutational and functional studies have identified important structural elements likely involved in the ion translocation by the SLC4 transporters.In the present article, we review the advances during the past decades in understanding the structure and function of the SLC4 transporters.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, Department of Biophysics and Molecular Physiology, School of Life Science and Technology, Huazhong University of Science and Technology Wuhan, China.

ABSTRACT
The solute carrier SLC4 family consists of 10 members, nine of which are [Formula: see text] transporters, including three Na(+)-independent Cl(-)/[Formula: see text] exchangers AE1, AE2, and AE3, five Na(+)-coupled [Formula: see text] transporters NBCe1, NBCe2, NBCn1, NBCn2, and NDCBE, as well as "AE4" whose Na(+)-dependence remains controversial. The SLC4 [Formula: see text] transporters play critical roles in pH regulation and transepithelial movement of electrolytes with a broad range of demonstrated physiological relevances. Dysfunctions of these transporters are associated with a series of human diseases. During the past decades, tremendous amount of effort has been undertaken to investigate the topological organization of the SLC4 transporters in the plasma membrane. Based upon the proposed topology models, mutational and functional studies have identified important structural elements likely involved in the ion translocation by the SLC4 transporters. In the present article, we review the advances during the past decades in understanding the structure and function of the SLC4 transporters.

No MeSH data available.


Related in: MedlinePlus