Warning: Undefined variable $zfal in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Deprecated: str_replace(): Passing null to parameter #3 ($subject) of type array|string is deprecated in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525

Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 530
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 531
  English Wikipedia
Nephropedia Template TP (
Twit Text
DeepDyve Pubget Overpricing |   
lüll Multi-domain misfolding: understanding the aggregation pathway of polyglutamine proteins Saunders HM; Bottomley SPProtein Eng Des Sel 2009[Aug]; 22 (8): 447-51The polyglutamine (polyQ) diseases consist of nine neurodegenerative diseases in which a polyQ tract expansion leads to protein misfolding and subsequent aggregation. Even when the causative proteins have the same length polyQ tract, there are differences in the severity and age of disease onset which implicate the polyQ flanking sequences as modulators of disease. Recent studies on the polyQ proteins ataxin-1, ataxin-3 and huntingtin exon-1 have shown that the flanking domains have an intrinsic ability to aggregate. This complex behavior leads to a multi-stage aggregation mechanism which we have termed multi-domain misfolding. In multi-domain misfolding, a flanking domain to the polyQ tract plays an early role in aggregation, before the contribution of the polyQ tract. A number of factors including the stability, dynamics and amyloidogenicity of the flanking domain modulate the impact on polyQ tract aggregation as well as any protein-protein interactions it undertakes. In this review, we examine the recent data in support of this novel mechanism of protein aggregation.|Amyloidosis/metabolism[MESH]|Animals[MESH]|Ataxin-1[MESH]|Ataxins[MESH]|Humans[MESH]|Models, Biological[MESH]|Nerve Tissue Proteins/chemistry/*metabolism[MESH]|Neurodegenerative Diseases/*metabolism[MESH]|Nuclear Proteins/metabolism[MESH]|Peptides/chemistry/*metabolism[MESH]|Protein Folding[MESH]|Protein Multimerization[MESH]|Transcription Factors/metabolism[MESH] |