Modeling Protein Homopolymeric Repeats: Possible Polyglutamine Structural Motifs for Huntington's Disease

Wedescribe a prototype system (Poly-X) for assisting an expert user in modelingprotein repeats. Poly-X reduces the large numberof degrees of freedomrequired to specify a protein motif in complete atomic detail. Theresult is a small numberof parameters that are easily understood by, and under the direct control of, a domain expert. The system was applied to the polyglutamine(poly-Q)repeat in the first exon huntingtin, the gene implicated in Huntington's disease. Wepresent four poly-Q structural motifs: twopoly-QfLsheet motifs(parallel and antiparallel) that constitute plausible alternatives to a similar previously published poly-Q/3-sheetmotif, and twonovel poly-Qhelix motifs(a-helix and 7r-helix). Toour knowledge,helical formsof polyglutamine have not been proposedbefore. Themotifs suggestthat there maybe several plausible aggregationstructures for the intranuclear inclusion bodies which have been found in diseased neurons, and mayhelp in the effort to understand the structural b...

• Type: Conference
• Year: 1998
• Where: ISMB
• Authors: Richard H. Lathrop, Malcolm S. Casale, Douglas J. Tobias, J. Lawrence Marsh, Leslie M. Thompson
• Keywords: Complete Atomic Detail, Computational Biology, ISMB 1998, Large Numberof Degrees, Poly-Q Structural Motifs