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Structural and molecular insights into the mechanism of action of human angiogenin-ALS variants in neurons.


Reference:

Thiyagarajan, N., Ferguson, R., Subramanian, V. and Acharya, K. R., 2012. Structural and molecular insights into the mechanism of action of human angiogenin-ALS variants in neurons. Nature Communications, 3, 1121.

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Official URL:

http://dx.doi.org/10.1038/ncomms2126

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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.

Details

Item Type Articles
CreatorsThiyagarajan, N., Ferguson, R., Subramanian, V. and Acharya, K. R.
DOI10.1038/ncomms2126
Related URLs
URLURL Type
http://www.scopus.com/inward/record.url?scp=84869481231&partnerID=8YFLogxKUNSPECIFIED
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493651/PubMedCentral
Uncontrolled Keywordsamyotrophic lateral sclerosis,angiogenin,neurons,stress granules,als mutants,crystal structure
DepartmentsFaculty of Science > Biology & Biochemistry
Research CentresCentre for Regenerative Medicine
RefereedYes
StatusPublished
ID Code32877

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