Testis-enhanced gene transfer family
Testis-enhanced gene transcript family | |||||||||
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Identifiers | |||||||||
Symbol | TEGT | ||||||||
Pfam | PF01027 | ||||||||
TCDB | 1.A.14 | ||||||||
OPM superfamily | 703 | ||||||||
OPM protein | 4pgr | ||||||||
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The testis-enhanced gene transcript (TEGT) family includes the testis-enhanced gene transcript proteins of mammals, which are expressed at high levels in the testis, the putative glutamate/aspartate binding proteins of plants and animals, the YccA protein of Escherichia coli and the YetJ protein of Bacillus subtilis. These proteins are about 200-250 residues in length and exhibit 7 TMSs.[1]
Homology
[edit]Homologues are found in a variety of Gram-negative and Gram-positive bacteria, yeast, fungi, plants, animals and viruses. The E. coli genome encodes three paralogues, YbhL, YbhM and YccA. Distant homologues found in Drosophilia melanogaster and the rat are the N-methyl-D-aspartate receptor-associated protein (NMDARAI) and the N-methyl-D-aspartate receptor glutamate binding chain, respectively. Two others are the rat neural membrane protein 35 and the Arabidopsis thaliana Bax inhibitor-1 (BI-1) protein capable of suppressing Bax-induced cell death in yeast.
BI-1
[edit]One of these proteins, TEGT or the Bax Inhibitor-1 (TC# 1.A.14.1.1), has a C-terminal domain that forms a Ca2+-permeable channel.[2] BI-1 is an ER-localized protein that protects against apoptosis and ER stress. BI-1 has been proposed to modulate ER Ca2+ homeostasis by acting as a Ca2+-leak channel. These proteins are distantly related to the ionotropic glutamate-binding protein of the N-methyl D-aspartate (NMDA) receptor of man. Homologues include a putative cold shock inducible protein and a SecY stabilizing protein.[1]
Function
[edit]Based on experimental determination of the BI-1 topology, Bultynck et al. proposes that its C-terminal α-helical 20 amino acid peptide catalyzes Ca2+ flux both in vivo and in vitro.[2] The Ca2+-leak properties were conserved among animal, but not plant and yeast orthologs. By mutating one of the critical aspartate residues (D213) in the proposed Ca2+-channel pore in full-length BI-1, D213 proved to be essential for BI-1 dependent ER Ca2+-leak.
Structure
[edit]Chang et al. published crystal structures of a bacterial homolog, YetJ (TC# 1.A.14.2.3) at 1.9 Å resolution and characterized its calcium leak activity. Its seven-transmembrane-helix fold features two triple-helix sandwiches wrapped around a central C-terminal helix.[3] Structures obtained in closed and open conformations are reversibly interconvertible by changes in the pH. A hydrogen-bonded perturbed pair of conserved aspartyl residues explains the pH dependence of this transition, and the pH regulates calcium influx in proteoliposomes. Homology models for human BI-1 provided insight into its cytoprotective activity.[3]
Transport Reaction
[edit]The generalized reaction catalyzed by TEGT channels is:
- cations (out) ⇌ cations (in)
References
[edit]- ^ a b van Stelten J, Silva F, Belin D, Silhavy TJ (August 2009). "Effects of antibiotics and a proto-oncogene homolog on destruction of protein translocator SecY". Science. 325 (5941): 753–6. Bibcode:2009Sci...325..753V. doi:10.1126/science.1172221. PMC 2832214. PMID 19661432.
- ^ a b Bultynck G, Kiviluoto S, Henke N, Ivanova H, Schneider L, Rybalchenko V, Luyten T, Nuyts K, De Borggraeve W, Bezprozvanny I, Parys JB, De Smedt H, Missiaen L, Methner A (January 2012). "The C terminus of Bax inhibitor-1 forms a Ca2+-permeable channel pore". The Journal of Biological Chemistry. 287 (4): 2544–57. doi:10.1074/jbc.M111.275354. PMC 3268414. PMID 22128171.
- ^ a b Chang Y, Bruni R, Kloss B, Assur Z, Kloppmann E, Rost B, Hendrickson WA, Liu Q (June 2014). "Structural basis for a pH-sensitive calcium leak across membranes". Science. 344 (6188): 1131–5. Bibcode:2014Sci...344.1131C. doi:10.1126/science.1252043. PMC 4119810. PMID 24904158.
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