Structural and functional analysis of the Josephin domain of the polyglutamine protein ataxin-3.
Ataxin-3 belongs to the family of polyglutamine proteins, which are associated with nine different neurodegenerative disorders. Relatively little is known about the structural and functional properties of ataxin-3, and only recently have these aspects of the protein begun to be explored. We have performed a preliminary investigation into the conserved N-terminal domain of ataxin-3, termed Josephin. We show that Josephin is a monomeric domain which folds into a globular conformation and possesses ubiquitin protease activity. In addition, we demonstrate that the presence of the polyglutamine region of the protein does not alter the structure of the protein. However, its presence destabilizes the Josephin domain. The implications of these data in the pathogenesis of polyglutamine repeat proteins are discussed.
Chow
Michelle K M
MK
Department of Biochemistry and Molecular Biology, P.O. Box 13D, Monash University, Vic. 3800, Australia.
Mackay
Joel P
JP
Whisstock
James C
JC
Scanlon
Martin J
MJ
Bottomley
Stephen P
SP
D000067699:Ataxin-3; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D017827:Machado-Joseph Disease / Q000235:genetics; D009682:Magnetic Resonance Spectroscopy; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D009687:Nuclear Proteins; D010455:Peptides / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins; D013816:Thermodynamics; D025801:Ubiquitin / Q000378:metabolism
D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; D012097:Repressor Proteins; D025801:Ubiquitin; C097188:polyglutamine; D010450:Endopeptidases; C092341:ATXN3 protein, human; D000067699:Ataxin-3