4AHJ

I46V - Angiogenin mutants and amyotrophic lateral sclerosis - a biochemical and biological analysis

Summary for 4AHJ

• Entry DOI: 10.2210/pdb4ahj/pdb
• Related: 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
• Descriptor: ANGIOGENIN, D(-)-TARTARIC ACID (3 entities in total)
• Functional Keywords: hydrolase, amyotrophic, lateral sclerosis, neovascularisation
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Secreted: P03950
• Total number of polymer chains: 1
• Total formula weight: 14304.11

Authors

Thiyagarajan, N.,Ferguson, R.,Saha, S.,Pham, T.,Subramanian, V.,Acharya, K.R. (deposition date: 2012-02-06, release date: 2012-10-10, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.032 Å)