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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.


Stereo view of cryo-EM structure of the TMD of human AE1 fitted with structural elements of chloride channel ClC. The dotted lines show the two V-shaped structures in the TMD of AE1 that fit well with helices B + C and J + K of ClC, respectively. The figure was modified from Yamaguchi et al. (2010b) with permission.
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Figure 4: Stereo view of cryo-EM structure of the TMD of human AE1 fitted with structural elements of chloride channel ClC. The dotted lines show the two V-shaped structures in the TMD of AE1 that fit well with helices B + C and J + K of ClC, respectively. The figure was modified from Yamaguchi et al. (2010b) with permission.

Mentions: Interestingly, a cryo-EM structure at a resolution of 7.5Å reveals that the TMD of human AE1 contains two V-shaped structures arranged in opposite direction to each other in the membrane (Figure 4; see Yamaguchi et al., 2010b). The authors therefore proposed that these two V-shaped structures represent two inverted repeats in AE1 TMD. Such inverted repeats are characteristic of a number of integral membrane transporters and channels (see review by Abramson and Wright, 2009), such as ClC chloride channel (Dutzler et al., 2002), uracil-H+ symporter UraA (Lu et al., 2011), Na+-galactose cotransporter vSGLT(Faham et al., 2008), Na+-leucine cotransporter LeuT (Yamashita et al., 2005), aquaporins (Murata et al., 2000; Sui et al., 2001), and glycerol facilitator GlpF (Fu et al., 2000). The TMDs of these integral membrane proteins usually contain an even number of transmembrane helices and have a pseudo two-fold symmetry (see review by Abramson and Wright, 2009). Some of these proteins (e.g., AQP1 and ClC) contain two half-helices in the membrane pointing to each other in opposite direction that play important roles in substrate binding or the formation of the ion selectivity filter (Murata et al., 2000; de Groot and Grubmuller, 2001; Dutzler et al., 2002).


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

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

Stereo view of cryo-EM structure of the TMD of human AE1 fitted with structural elements of chloride channel ClC. The dotted lines show the two V-shaped structures in the TMD of AE1 that fit well with helices B + C and J + K of ClC, respectively. The figure was modified from Yamaguchi et al. (2010b) with permission.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664831&req=5

Figure 4: Stereo view of cryo-EM structure of the TMD of human AE1 fitted with structural elements of chloride channel ClC. The dotted lines show the two V-shaped structures in the TMD of AE1 that fit well with helices B + C and J + K of ClC, respectively. The figure was modified from Yamaguchi et al. (2010b) with permission.
Mentions: Interestingly, a cryo-EM structure at a resolution of 7.5Å reveals that the TMD of human AE1 contains two V-shaped structures arranged in opposite direction to each other in the membrane (Figure 4; see Yamaguchi et al., 2010b). The authors therefore proposed that these two V-shaped structures represent two inverted repeats in AE1 TMD. Such inverted repeats are characteristic of a number of integral membrane transporters and channels (see review by Abramson and Wright, 2009), such as ClC chloride channel (Dutzler et al., 2002), uracil-H+ symporter UraA (Lu et al., 2011), Na+-galactose cotransporter vSGLT(Faham et al., 2008), Na+-leucine cotransporter LeuT (Yamashita et al., 2005), aquaporins (Murata et al., 2000; Sui et al., 2001), and glycerol facilitator GlpF (Fu et al., 2000). The TMDs of these integral membrane proteins usually contain an even number of transmembrane helices and have a pseudo two-fold symmetry (see review by Abramson and Wright, 2009). Some of these proteins (e.g., AQP1 and ClC) contain two half-helices in the membrane pointing to each other in opposite direction that play important roles in substrate binding or the formation of the ion selectivity filter (Murata et al., 2000; de Groot and Grubmuller, 2001; Dutzler et al., 2002).

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.