Details:

Alternative Title:
Biochemistry
Personal Author:
Vuković, Lela ; Koh, Hye Ran ; Myong, Sua ; Schulten, Klaus
Vuković, Lela ; Koh, Hye Ran ; Myong, Sua ; Schulten, Klaus Less -
Description:
Recognition of double-stranded (ds) RNA is an important part of many cellular pathways, including RNA silencing, viral recognition, RNA editing, processing, and transport. dsRNA recognition is often achieved by dsRNA binding domains (dsRBDs). We use atomistic molecular dynamics simulations to examine the binding interface of the transactivation response RNA binding protein (TRBP) dsRBDs to dsRNA substrates. Our results explain the exclusive selectivity of dsRBDs toward dsRNA and against DNA-RNA hybrid and dsDNA duplexes. We also provide corresponding experimental evidence. The dsRNA duplex is recognized by dsRBDs through the A-form of three duplex grooves and by the chemical properties of RNA bases, which have 2'-hydroxyl groups on their sugar rings. Our simulations show that TRBP dsRBD discriminates dsRNA- from DNA-containing duplexes primarily through interactions at two duplex grooves. The simulations also reveal that the conformation of the DNA-RNA duplex can be altered by dsRBD proteins, resulting in a weak binding of dsRBDs to DNA-RNA hybrids. Our study reveals the structural and molecular basis of protein-RNA interaction that gives rise to the observed substrate specificity of dsRNA binding proteins.
Subjects:
[+]
Amino Acid Sequence Article Binding Sites DNA Molecular Dynamics Simulation Molecular Sequence Data Nucleic Acid Conformation Nucleic Acid Heteroduplexes Protein Structure, Tertiary RNA, Double-Stranded RNA-Binding Proteins
Source:
Biochemistry. 2014; 53(21):3457-3466.
Pubmed ID:
24801449
Pubmed Central ID:
PMC4051425
Document Type:
Journal Article
Funding:
1DP2GM105453/DP/NCCDPHP CDC HHS/United States ; 9P41GM104601/GM/NIGMS NIH HHS/United States ; P41 GM104601/GM/NIGMS NIH HHS/United States
1DP2GM105453/DP/NCCDPHP CDC HHS/United States ; 9P41GM104601/GM/NIGMS NIH HHS/United States ; P41 GM104601/GM/NIGMS NIH HHS/United States Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:4f58890d1c6f1004b23a3e8d342ebbe2f1f623365958785a16932927e4e05ee6
Download URL:
https://stacks.cdc.gov/view/cdc/31006/cdc_31006_DS1.pdf
File Type:

Supporting Files

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