NR AFMA
AU Hollenbach,B.; Scherzinger,E.; Schweiger,K.; Lurz,R.; Lehrach,H.; Wanker,E.E.
TI Aggregation of truncated GST-HD exon 1 fusion proteins containing normal range and expanded glutamine repeats
QU Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 1999 Jun 29; 354(1386): 991-4
PT journal article
AB We have shown previously by electron microscopy that the purified glutathione S-transferase (GST)-Huntington's disease (HD) exon 1 fusion protein with 51 glutamine residues (GST-HD51) is an oligomer, and that site-specific proteolytic cleavage of this fusion protein results in the formation of insoluble more highly ordered protein aggregates with a fibrillar or ribbon-like morphology (E. Scherzinger et al. (1997) Cell 90, 549-558). Here we report that a truncated GST HD exon 1 fusion protein with 51 glutamine residues, which lacks the proline-rich region C-terminal to the polyglutamine (polyQ) tract (GST-HD51 delta P) self-aggregates into high-molecular-mass protein aggregates without prior proteolytic cleavage. Electron micrographs of these protein aggregates revealed thread-like fibrils with a uniform diameter of ca. 25 nm. In contrast, proteolytic cleavage of GST-HD51 delta P resulted in the formation of numerous clusters of high-molecular-mass fibrils with a different, ribbon-like morphology. These structures were reminiscent of prion rods and beta-amyloid fibrils in Alzheimer's disease. In agreement with our previous results with full-length GST-HD exon 1, the truncated fusion proteins GST-HD20 delta P and GST-HD30 delta P did not show any tendency to form more highly ordered structures, either with or without protease treatment.
MH Cloning, Molecular; Escherichia coli; Exons; Glutathione Transferase/genetics/metabolism; Human; Huntington Disease/genetics; Microscopy, Electron; Nerve Tissue Proteins/*genetics/*metabolism/ultrastructure; Nuclear Proteins/*genetics/*metabolism/ultrastructure; Recombinant Fusion Proteins/isolation &; purification/metabolism/ultrastructure; Sequence Deletion; Support, Non-U.S. Gov't; Trinucleotide Repeat Expansion/*genetics
AD Max-Planck-Institut für Molekulare Genetik, Berlin, Germany.
SP englisch
PO England