AAA(+) ATPase;
early onset torsion dystonia;
endoplasmic reticulum;
membrane protein;
signal peptide;
torsinA;
D O I:
10.1042/BJ20061313
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
TorsinA is a widely expressed AAA(+) (ATPases associated with various cellular activities) ATPase of unknown function. Previous studies have described torsinA as a type II protein with a cleavable signal sequence, a single membrane spanning domain, and its C-terminus located in the ER (endoplasmic reticulum) lumen. However, in the present study we show that torsinA is not in fact an integral membrane protein. Instead we find that the mature protein associates peripherally with the ER membrane, most likely through an interaction with an integral membrane protein. Consistent with this model, we provide evidence that the signal peptidase complex cleaves the signal sequence of torsinA, and we show that the region previously suggested to form a transmembrane domain is translocated into the lumen of the ER. The finding that torsinA is a peripheral, and not an integral membrane protein as previously thought, has important implications for understanding the function of this novel ATPase.
机构:
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Mol Neurogenet Unit, Boston, MA 02129 USAHarvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Mol Neurogenet Unit, Boston, MA 02129 USA
Breakefield, XO
;
Kamm, C
论文数: 0引用数: 0
h-index: 0
机构:Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Mol Neurogenet Unit, Boston, MA 02129 USA
Kamm, C
;
Hanson, PI
论文数: 0引用数: 0
h-index: 0
机构:Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Mol Neurogenet Unit, Boston, MA 02129 USA
机构:
Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA
Hanson, PI
;
Whiteheart, SW
论文数: 0引用数: 0
h-index: 0
机构:Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA
机构:
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Mol Neurogenet Unit, Boston, MA 02129 USAHarvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Mol Neurogenet Unit, Boston, MA 02129 USA
Breakefield, XO
;
Kamm, C
论文数: 0引用数: 0
h-index: 0
机构:Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Mol Neurogenet Unit, Boston, MA 02129 USA
Kamm, C
;
Hanson, PI
论文数: 0引用数: 0
h-index: 0
机构:Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Mol Neurogenet Unit, Boston, MA 02129 USA
机构:
Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA
Hanson, PI
;
Whiteheart, SW
论文数: 0引用数: 0
h-index: 0
机构:Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA