Expression and characterization of full-length human huntingtin, an elongated HEAT repeat protein.
Huntington disease is an inherited neurodegenerative disorder that is caused by expanded CAG trinucleotide repeats, resulting in a polyglutamine stretch of >37 on the N terminus of the protein huntingtin (htt). htt is a large (347 kDa), ubiquitously expressed protein. The precise functions of htt are not clear, but its importance is underscored by the embryonic lethal phenotype in htt knock-out mice. Despite the fact that the htt gene was cloned 13 years ago, little is known about the properties of the full-length protein. Here we report the expression and preliminary characterization of recombinant full-length wild-type human htt. Our results support a model of htt composed entirely of HEAT repeats that stack to form an elongated superhelix.
Li
Wei
W
Department of Haematology, University of Cambridge, Cambridge Institute for Medical Research, Cambridge CB2 2XY, United Kingdom.
Serpell
Louise C
LC
Carter
Wendy J
WJ
Rubinsztein
David C
DC
Huntington
James A
JA
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002850:Chromatography, Gel; D002942:Circular Dichroism; D003001:Cloning, Molecular; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D000071058:Huntingtin Protein; D007313:Insecta; D008854:Microscopy, Electron; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism / Q000648:ultrastructure
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins