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Structural Biology 2018
Volume: 4
Biochemistry & Molecular Biology Journal
Page 68
March 15-16 2018
Barcelona, Spain
10
th
Edition of International Conference on
Structural Biology
T
he sodium-driven chloride/bicarbonate exchanger (NDCBE) is
a member of the sodium-bicarbonate co-transporters (NBCs)
withinthesolutecarrier4(SLC4)genefamilyandmainlyexpressed
in the brain, especially in the choroid plexus. NDCBE is primarily
associated with the presynaptic vesicles of glutamatergic and
GABAergic neurons; Zn has been shown to accumulate in
presynaptic vesicles of glutamatergic neurons and efflux from the
cytoplasm to the vesicle is facilitated by the membrane exporter
ZnT-3. The glutamatergic neurons are found cerebral cortex and
may be critical for cognitive and emotional functioning. The
trace element Zn is vital for life and involved in several functional
and catalytic binding sites in enzymes and proteins regulating
physiological processes. In the brain, zinc dependent processes
include central nervous system development, and neuronal
modulation. The crystal structure at 2.8 Å resolution of the
regulatory N-terminal domain of human NDCBE represents the
first crystal structure of an electroneutral sodium-bicarbonate
co-transporter. A novel conserved Zn-binding motif present in
the N-terminal domain of NDCBE is identified and characterized
in vitro
. The Zn site is mapped to a cluster of histidines close
to the conserved ETARWLKFEE motif and is likely involved with
regulation of this important motif. The combined structural and
bioinformatics analysis provides a model that predicts, with
additional confidence, the physiologically relevant interface
between the cytoplasmic domain and the transmembrane
domain. As even small variations in concentration of the
intracellular Zn would affect the equilibrium between the histidine
binding sites and free Zn ions, we hypothesize that this site would
consequently act as a pH sensor.
j.p.morth@ncmm.uio.noZink binding site mapped on the crystal structure of the
regulatory domain of the human sodium-driven chloride/
bicarbonate exchanger
Morth J P, Alvadia C M, Sommer T, Bjerregaard-Andersen K, Damkier H H,
Montrasio M
and
Aalkjaer C
University of Oslo, Norway
Biochem Mol biol J, Volume 4
DOI: 10.21767/2471-8084-C1-009