ICS Theory Group

ICS 269, Spring 1998: Theory Seminar

13 February 1997:
Possible polyglutamine structural motifs for Huntington's disease
Mac Casale, ICS, UC Irvine

We describe a prototype system (Poly-X) for assisting an expert user in modeling protein repeats. Poly-X reduces the large number of degrees of freedom required to specify a protein motif in complete atomic detail. The result is a small number of parameters that are easily understood by, and directly under the control of, a domain expert. The system was applied to the poly-glutamine (poly-Q) repeat in the first exon of huntingtin, a gene region implicated in Huntington's disease. We present four poly-Q structural motifs: two poly-Q beta-sheet motifs (parallel and anti-parallel) that constitute plausible alternatives to a previously published poly-Q beta-sheet motif, and two novel poly-Q helices (alpha-helix and pi-helix). The motifs suggest that there may be several plausible aggregation structures for intranuclear inclusion bodies, and may help in the effort to understand the structural basis for Huntington's disease.