Polyglutamine dances the conformational cha-cha-cha

Abstract

While polyglutamine repeats appear in dozens of human proteins, high-resolution structural analysis of these repeats in their native context has eluded researchers. Kim et al. now describe multiple crystal structures and demonstrate that polyglutamine in huntingtin dances through multiple conformations.

Figure 1. Conformational Cha-cha-cha: X-Ray Crystallography Reveals That PolyQ and Polyproline Adopt Multiple Conformations in Htt Exon1

(A) Four a helices are shown. Each extends from the N-terminal residue of the N¹⁷ region (Met 371-Phe 387) of Htt Exon1 (blue) and continues as a helix for a varying number of glutamine residues (cyan = 5, yellow = 9, magenta = 12, and salmon = 15). Glutamines C-terminal to the a-helical structured residues may adopt other conformations, including random coil, extended loop, or b strand. (B) Five of the seven observed polyproline regions of Htt Exon1 are shown superimposed on their five C-terminal residues. Note that all demonstrate a proline-helix conformation, but some are kinked while others are extended. This figure was generated using PyMol (www.pymol.org).