4AHG: S28n - Angiogenin Mutants And Amyotrophic Lateral Sclerosis - A Biochemical And Biological Analysis

Citation:
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.
PDB ID: 4AHGDownload
MMDB ID: 103743
PDB Deposition Date: 2012/2/6
Updated in MMDB: 2012/10
Experimental Method:
x-ray diffraction
Resolution: 2.45  Å
Source Organism:
Similar Structures:
Biological Unit for 4AHG: monomeric; determined by author and by software (PISA)
Molecular Components in 4AHG
Label Count Molecule
Protein (1 molecule)
1
Angiogenin(Gene symbol: ANG)
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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