1SOQ

Crystal structure of the transthyretin mutant A108Y/L110E solved in space group C2

1SOQ の概要

• エントリーDOI: 10.2210/pdb1soq/pdb
• 関連するPDBエントリー: 1F41 1SOK
• 分子名称: Transthyretin (2 entities in total)
• 機能のキーワード: greek key beta barrel, transport protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 55541.65

構造登録者

Hornberg, A.,Olofsson, A.,Eneqvist, T.,Lundgren, E.,Sauer-Eriksson, A.E. (登録日: 2004-03-15, 公開日: 2004-07-06, 最終更新日: 2023-08-23)

主引用文献

Hornberg, A.,Olofsson, A.,Eneqvist, T.,Lundgren, E.,Sauer-Eriksson, A.E.
The beta-strand D of transthyretin trapped in two discrete conformations
Biochim.Biophys.Acta, 1700:93-104, 2004

PubMed Abstract: Conformational changes in native and variant forms of the human plasma protein transthyretin (TTR) induce several types of amyloid diseases. Biochemical and structural studies have mapped the initiation site of amyloid formation onto residues at the outer C and D beta-strands and their connecting loop. In this study, we characterise an engineered variant of transthyretin, Ala108Tyr/Leu110Glu, which is kinetically and thermodynamically more stable than wild-type transthyretin, and as a consequence less amyloidogenic. Crystal structures of the mutant were determined in two space groups, P2(1)2(1)2 and C2, from crystals grown in the same crystallisation set-up. The structures are identical with the exception for residues Leu55-Leu58, situated at beta-strand D and the following DE loop. In particular, residues Leu55-His56 display large shifts in the C2 structure. There the direct hydrogen bonding between beta-strands D and A has been disrupted and is absent, whereas the beta-strand D is present in the P2(1)2(1)2 structure. This difference shows that from a mixture of metastable TTR molecules, only the molecules with an intact beta-strand D are selected for crystal growth in space group P2(1)2(1)2. The packing of TTR molecules in the C2 crystal form and in the previously determined amyloid TTR (ATTR) Leu55Pro crystal structure is close-to-identical. This packing arrangement is therefore not unique in amyloidogenic mutants of TTR.

PubMed: 15210129
DOI: 10.1016/j.bbapap.2004.04.004

実験手法

X-RAY DIFFRACTION (2.1 Å)