Disease-associated polyglutamine stretches in monomeric huntingtin adopt a compact structure.
Disease-associated polyglutamine stretches in monomeric huntingtin adopt a compact structure.
复制标题
DOI：
10.1016/j.jmb.2012.01.034
复制
发表时间：
2012-08-24
影响因子：
5.6
通讯作者：
Finkbeiner, Steven
中科院分区：
文献类型：
--
作者：
Peters-Libeu, Clare;Miller, Jason;Rutenber, Earl;Newhouse, Yvonne;Krishnan, Preethi;Cheung, Kenneth;Hatters, Danny;Brooks, Elizabeth;Widjaja, Kartika;Tina Tran;Mitra, Siddhartha;Arrasate, Montserrat;Mosquera, Luis A.;Taylor, Dean;Weisgraber, Karl H.;Finkbeiner, Steven
Abnormal *polyglutamine (polyQ) tracts are the only common feature in nine proteins that each cause a dominant neurodegenerative disorder. In Huntington’s disease (HD), tracts longer than 36 glutamines in the protein huntingtin (htt) cause degeneration. In situ, monoclonal antibody 3B5H10 binds to different htt fragments in neurons in proportion to their toxicity. Here, we determined the structure of the 3B5H10 Fab to 1.9Å by x-ray crystallography. Modeling demonstrates that the paratope forms a groove suitable for binding two β-rich polyQ strands. Using small-angle x-ray scattering (SAXS), we confirmed that the polyQ epitope recognized by 3B5H10 is a compact, two-stranded hairpin within monomeric htt and is abundant in htt fragments unbound to antibody. Thus, disease-associated polyQ stretches preferentially adopt compact conformations. Since 3B5H10 binding predicts degeneration, this compact polyQ structure may be neurotoxic.
登录
查看更多内容
DOI：
10.1016/j.str.2009.08.002
发表时间：
2009-09-09
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
Kim MW;Chelliah Y;Kim SW;Otwinowski Z;Bezprozvanny I
通讯作者：
Bezprozvanny I
影响因子：
5.6
作者：
Klein, Fabrice A. C.;Pastore, Annalisa;Trottier, Yvon
通讯作者：
Trottier, Yvon
影响因子：
6.1
作者：
Konarev, PV;Volkov, VV;Svergun, DI
通讯作者：
Svergun, DI
DOI：
10.1111/j.1432-1033.1994.00099.x
发表时间：
1994-10-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
KLINZ, FJ
通讯作者：
KLINZ, FJ
影响因子：
11.4
作者：
LESCURE, A;LUTZ, Y;TORA, L
通讯作者：
TORA, L