A two-domain elevator mechanism for sodium/proton antiport

Lee, Chiara; Kang, Hae Joo; Ballmoos, Christoph von; Newstead, Simon; Uzdavinys, Povilas; Dotson, David; Iwata, So; Beckstein, Oliver; Cameron, Alexander D.; Drew, David

doi:10.1016/j.bbabio.2014.05.250

Cited by 49 publications

(109 citation statements)

References 27 publications

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“…3c) along which the transport domain can move. The elevator mechanism is considered to be a manifestation of the 'moving-carrier mechanism' [42][43][44][45][46] .…”

Section: Transport Mechanismmentioning

confidence: 99%

Structural and mechanistic insights into prokaryotic energy-coupling factor transporters

Slotboom

2013

Nat Rev Microbiol

118

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“…3c) along which the transport domain can move. The elevator mechanism is considered to be a manifestation of the 'moving-carrier mechanism' [42][43][44][45][46] .…”

Section: Transport Mechanismmentioning

confidence: 99%

Structural and mechanistic insights into prokaryotic energy-coupling factor transporters

Slotboom

2013

Nat Rev Microbiol

118

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“…A comprehensive description of these is clearly beyond the scope of this review [13]. The precise structure of NHE1 (or of any other mammalian NHE) is not known, but the structures of two bacterial homologues, NhaA of E. coli and NapA of T. thermophilus have been determined [71,89]. A recent review describes the current structural model of NHE1 [88].…”

Section: Slc9a1-nhe1mentioning

confidence: 99%

Traditional and emerging roles for the SLC9 Na+/H+ exchangers

Fuster

Alexander

2013

Pflugers Arch - Eur J Physiol

137

121

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The SLC9 gene family encodes Na + /H + exchangers (NHEs). These transmembrane proteins transport ions across lipid bilayers in a diverse array of species from prokaryotes to eukaryotes, including plants, fungi and animals. They utilize the electrochemical gradient of one ion to transport another ion against its electrochemical gradient. Currently, 13 evolutionarily conserved NHE isoforms are known in mammals [46,22,128]. The SLC9 gene family (solute carrier classification of transporters:www.bioparadigms.org) is divided into three subgroups [46]. The SLC9A subgroup encompasses plasmalemmal isoforms NHE1-5 (SLC9A1-5) and the predominantly intracellular isoforms NHE6-9 (SLC9A6-9). The SLC9B subgroup consists of two recently cloned isoforms, NHA1 and NHA2 (SLC9B1 and SLC9B2, respectively). The SLC9C subgroup consist of a sperm specific plasmalemmal NHE (SLC9C1) and a putative NHE, SLC9C2, for which there is currently no functional data [46].NHEs participate in the regulation of cytosolic and organellar pH as well as cell volume. In the intestine and kidney, NHEs are critical for transepithelial movement of Na + and HCO 3 -and thus for whole body volume and acid-base homeostasis [46]. Mutations in the NHE6 or NHE9 genes cause neurological disease in humans and are currently the only NHEs directly linked to human disease.However, it is becoming increasingly apparent that members of this gene family contribute to the pathophysiology of multiple human diseases.

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“…Interestingly, the Na + /H + antiporter structures that share the NhaA fold are characterized by different numbers of TMs from 12 to 13 (16,17,19) and are dimeric like Ec-NhaA. However, two prokaryotic ASBT (apical sodium-dependent bile acid transporter, also known as SLC10A2) symporters share the NhaA fold but have only 10 TMs; they lack the Ec-NhaA equivalents of helices VI and VII (20,21).…”

Section: /Hmentioning

confidence: 99%

NhaA antiporter functions using 10 helices, and an additional 2 contribute to assembly/stability

Padan

Danieli

Keren

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The Escherichia coli Na + /H + antiporter (Ec-NhaA) is the best-characterized of all pH-regulated Na + /H + exchangers that control cellular Na + and H + homeostasis. Ec-NhaA has 12 helices, 2 of which (VI and VII) are absent from other antiporters that share the EcNhaA structural fold. This α-hairpin is located in the dimer interface of the Ec-NhaA homodimer together with a β-sheet. Here we examine computationally and experimentally the role of the α-hairpin in the stability, dimerization, transport, and pH regulation of Ec-NhaA. Evolutionary analysis (ConSurf) indicates that the VI-VII helical hairpin is much less conserved than the remaining transmembrane region. Moreover, normal mode analysis also shows that intact NhaA and a variant, deleted of the α-hairpin, share similar dynamics, suggesting that the structure may be dispensable. Thus, two truncated Ec-NhaA mutants were constructed, one deleted of the α-hairpin and another also lacking the β-sheet. The mutants were studied at physiological pH in the membrane and in detergent micelles. The findings demonstrate that the truncated mutants retain significant activity and regulatory properties but are defective in the assembly/stability of the Ec-NhaA dimer.

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A two-domain elevator mechanism for sodium/proton antiport

Cited by 49 publications

References 27 publications

Structural and mechanistic insights into prokaryotic energy-coupling factor transporters

Structural and mechanistic insights into prokaryotic energy-coupling factor transporters

Traditional and emerging roles for the SLC9 Na+/H+ exchangers

NhaA antiporter functions using 10 helices, and an additional 2 contribute to assembly/stability

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