8JNU

Crystal structure of V30G mutated human transthyretin

8JNU の概要

• エントリーDOI: 10.2210/pdb8jnu/pdb
• 分子名称: Transthyretin, MAGNESIUM ION (3 entities in total)
• 機能のキーワード: transport of thyroid hormone, transport protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 29843.88

構造登録者

Mizuguchi, M.,Yamada, S.,Obita, T. (登録日: 2023-06-06, 公開日: 2024-04-17, 最終更新日: 2024-05-01)

主引用文献

Mizuguchi, M.,Obita, T.,Yamada, S.,Nabeshima, Y.
Trypsin-induced aggregation of transthyretin Valine 30 variants associated with hereditary amyloidosis.
Febs J., 291:1732-1743, 2024

PubMed Abstract: Amyloid fibrils of transthyretin (TTR) consist of full-length TTR and C-terminal fragments starting near residue 50. However, the molecular mechanism underlying the production of the C-terminal fragment remains unclear. Here, we investigated trypsin-induced aggregation and urea-induced unfolding of TTR variants associated with hereditary amyloidosis. Trypsin strongly induced aggregation of variants V30G and V30A, in each of which Val30 in the hydrophobic core of the monomer was mutated to less-bulky amino acids. Variants V30L and V30M, in each of which Val30 was mutated to bulky amino acids, also exhibited trypsin-induced aggregation. On the other hand, pathogenic variant I68L as well as the nonpathogenic V30I did not exhibit trypsin-induced aggregation. The V30G variant was extremely unstable compared with the other variants. The V30G mutation caused the formation of a cavity and the rearrangement of Leu55 in the hydrophobic core of the monomer. These results suggest that highly destabilized transthyretin variants are more susceptible to trypsin digestion.

PubMed: 38273457
DOI: 10.1111/febs.17070

実験手法

X-RAY DIFFRACTION (1.64 Å)