Disease relevance of Thr-Gly

• To investigate the molecular mechanisms of the 'gain of toxic function' of mutant Cu/Zn superoxide dismutase (SOD) associated with familial amyotrophic lateral sclerosis (FALS), mutant (Ala 4 --> Thr, Gly 85 --> Arg, Gly 93 --> Ala, and two base-pair deletion in the 126th codon), as well as wild-type (wt), Cu/Zn SODs were expressed in COS7 cells [1].
• The key component in the fusion is the catalytic core of sortase A from Staphylococcus aureus (SrtAc), which recognizes and cleaves the Thr-Gly bond at an LPXTG sequence with moderate activity [2].
• Various tRNA transcripts were constructed to study the identity elements of E. coli tRNAs (Arg, Lys, Ala, Trp, Thr, Gly, Ser, Asn, Cys, His) [3].

High impact information on Thr-Gly

• This phenomenon provides a selective explanation for the geographical distribution of Thr-Gly lengths and gives a rare glimpse of the interplay between molecular polymorphism, behavior, population biology, and natural selection [4].
• The deletion changes the amino acid sequence at position 899 substituting Arg for a Thr-Gly [5].
• In D. melanogaster, this region is replaced by a dipeptide Thr-Gly repeat, which plays a role in the thermal stability of the circadian phenotype [6].
• The results are consistent with the view that selection may be operating on various haplotypes which share the Thr-Gly length alleles encoding 17, 20 and 23 dipeptide pairs, and that the repeat itself may be the focus for selection [7].
• Consequently, the Thr-Gly repeat does not have a mutation rate that is as high as some of the non-coding minisatellites, but it is several orders of magnitude higher than the nucleotide substitution rate [7].

Biological context of Thr-Gly

• Using chimeric per transgenes which carry the different species Thr-Gly fragments, we have been able to identify components of the behaviour that are modulated by this region of the PER protein [8].
• It has previously been shown that Thr-Gly repeat length variation at the period gene affects song traits in D. melanogaster, which gives the repetitive regions a special interest [9].
• In Drosophila simulans, balancing selection appears to maintain a polymorphism in this region, with three repeat lengths carrying 23, 24 or 25 Thr-Gly pairs, each in complete linkage disequilibrium with a distinctive flanking region amino acid moiety [10].

Associations of Thr-Gly with other chemical compounds

• The study of amino acid repartition between liver and plasma with different diets indicates that transport could modulate utilization of Ala, Ser, Thr, Gly, Gln, and Asp [11].

Gene context of Thr-Gly

• Two alternatively spliced IGF1R mRNA transcripts have been described to differ by only three nucleotides (CAG) in the coding sequence, resulting in an amino-acid change from the originally described Thr-Gly to an Arg in the extracellular portion of the receptor beta subunit [12].
• N-Acetyl derivatives of Asn, Gln, Ser, Thr, Gly, Ala, Tyr, Pro, Met, Val, Ile and Leu as well as N-formyl-Met could be separated and identified in the same chromatographic run [13].
• Clinal variation for repeat number in the Thr-Gly region of the period circadian timing gene in Drosophila melanogaster was described in Europe and has subsequently been used as evidence of thermal selection on period alleles [14].

Analytical, diagnostic and therapeutic context of Thr-Gly

• The threonine-glycine (Thr-Gly) repeat region of the period (per) gene of eight natural populations of Drosophila simulans from Europe and North Africa was analyzed by polymerase chain reaction, DNA sequencing and heteroduplex formation [15].

References