4DCQ

Crystal Structure of the Fab Fragment of 3B5H10, an Antibody-Specific for Extended Polyglutamine Repeats (orthorhombic form)

4DCQ の概要

• エントリーDOI: 10.2210/pdb4dcq/pdb
• 関連するPDBエントリー: 3S96
• 分子名称: 3B5H10 FAB Light Chain, 3B5H10 FAB Heavy Chain, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: fab fragment, immunoglobulin domain, anti-polyglutamine, polyglutamine repeats, immune system
• 由来する生物種: Mus musculus (mouse); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 47223.02

構造登録者

Peters-Libeu, C.A.,Tran, T.,Finkbeiner, S.,Weisgraber, K. (登録日: 2012-01-18, 公開日: 2012-02-22, 最終更新日: 2024-10-16)

主引用文献

Peters-Libeu, C.,Miller, J.,Rutenber, E.,Newhouse, Y.,Krishnan, P.,Cheung, K.,Hatters, D.,Brooks, E.,Widjaja, K.,Tran, T.,Mitra, S.,Arrasate, M.,Mosquera, L.A.,Taylor, D.,Weisgraber, K.H.,Finkbeiner, S.
Disease-associated polyglutamine stretches in monomeric huntingtin adopt a compact structure.
J.Mol.Biol., 421:587-600, 2012

PubMed Abstract: Abnormal polyglutamine (polyQ) tracts are the only common feature in nine proteins that each cause a dominant neurodegenerative disorder. In Huntington's disease, 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 3B5H10 Fab to 1.9 Å resolution 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, 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.

PubMed: 22306738
DOI: 10.1016/j.jmb.2012.01.034

実験手法

X-RAY DIFFRACTION (1.94 Å)