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.