4AOH

Structural snapshots and functional analysis of human angiogenin variants associated with Amyotrophic Lateral Sclerosis (ALS)

4AOH の概要

• エントリーDOI: 10.2210/pdb4aoh/pdb
• 関連するPDBエントリー: 1A4Y 1ANG 1AWZ 1B1E 1B1I 1B1J 1H0D 1H52 1H53 1HBY 1K58 1K59 1K5A 1K5B 1UN3 1UN4 1UN5 2ANG 4AHD 4AHE 4AHF 4AHG 4AHH 4AHI 4AHJ 4AHK 4AHL 4AHM 4AHN
• 分子名称: ANGIOGENIN, D(-)-TARTARIC ACID, L(+)-TARTARIC ACID, ... (4 entities in total)
• 機能のキーワード: hydrolase, angiogenesis, neovascularisation, amyotropic lateral sclerosis, als, motor neuron disease, ribonuclease inhibitor, nuclear localisation, nuclear localization
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Secreted: P03950
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14540.29

構造登録者

Thiyagarajan, N.,Ferguson, R.,Subramanian, V.,Acharya, K.R. (登録日: 2012-03-27, 公開日: 2012-10-10, 最終更新日: 2024-10-16)

主引用文献

Thiyagarajan, N.,Ferguson, R.,Subramanian, V.,Acharya, K.R.
Structural and Molecular Insights Into the Mechanism of Action of Human Angiogenin-Als Variants in Neurons
Nat.Commun., 3:1121-, 2012

PubMed Abstract: Mutations in angiogenin (ANG), a member of the ribonuclease A superfamily, are associated with amyotrophic lateral sclerosis (ALS; sporadic and familial) and Parkinson's disease. We have previously shown that ANG is expressed in neurons during neuro-ectodermal differentiation, and that it has both neurotrophic and neuroprotective functions. Here we report the atomic resolution structure of native ANG and 11 ANG-ALS variants. We correlate the structural changes to the effects on neuronal survival and the ability to induce stress granules in neuronal cell lines. ANG-ALS variants that affect the structure of the catalytic site and either decrease or increase the RNase activity affect neuronal survival. Neuronal cell lines expressing the ANG-ALS variants also lack the ability to form stress granules. Our structure-function studies on these ANG-ALS variants are the first to provide insights into the cellular and molecular mechanisms underlying their role in ALS.

PubMed: 23047679
DOI: 10.1038/NCOMMS2126

実験手法

X-RAY DIFFRACTION (1.041 Å)