Sheep have an unusual variant of the brain-specific metallothionein, metallothionein-III.
Sheep metallothionein-III (MT-III) cDNA was isolated from a brain cDNA library and characterized. In contrast with MT-III from other species, sheep MT-III cDNA is predicted to encode a protein with significantly different metal-binding properties, owing to the loss of three of its cysteine residues. RT-PCR from other sheep confirmed that this aberrant structure is ubiquitous in this species. MT-III was successfully isolated from sheep brain, demonstrating that the cDNA does give rise to a protein product of the predicted structure. Sheep MT-III is similar to other mammalian MT-IIIs in that it retains the Cys-Pro-Cys-Pro motif which is thought to encode growth-inhibitory activity, and we show that it is likewise able to inhibit neuron survival in vitro. This is the first naturally occurring variant of MT-III (or any other major mammalian MT gene) which gives rise to a protein product. These findings are discussed in light of proposed roles of MT in the mammalian brain.
Chung
Roger S
RS
Discipline of Biochemistry, University of Tasmania, Hobart, GPO Box 252-58, Tasmania, 7001, Australia.
Holloway
Adele F
AF
Eckhardt
Bedrich L
BL
Harris
Julie A
JA
Vickers
James C
JC
Chuah
Meng Inn
MI
West
Adrian K
AK
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D014644:Genetic Variation; D006801:Humans; D000090023:Metallothionein 3; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012756:Sheep / Q000235:genetics* / Q000378:metabolism*; D014018:Tissue Distribution
D018076:DNA, Complementary; D000090023:Metallothionein 3; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins