Title | Structure of human RNase L reveals the basis for regulated RNA decay in the IFN response. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Han, Y, Donovan, J, Rath, S, Whitney, G, Chitrakar, A, Korennykh, A |
Journal | Science |
Volume | 343 |
Issue | 6176 |
Pagination | 1244-8 |
Date Published | 2014 Mar 14 |
ISSN | 1095-9203 |
Keywords | Crystallography, X-Ray, Endoribonucleases, HeLa Cells, Hepatitis B virus, Humans, Interferon Type I, Protein Multimerization, Protein Structure, Tertiary, RNA Cleavage, RNA Stability, RNA, Viral |
Abstract | <p>One of the hallmark mechanisms activated by type I interferons (IFNs) in human tissues involves cleavage of intracellular RNA by the kinase homology endoribonuclease RNase L. We report 2.8 and 2.1 angstrom crystal structures of human RNase L in complexes with synthetic and natural ligands and a fragment of an RNA substrate. RNase L forms a crossed homodimer stabilized by ankyrin (ANK) and kinase homology (KH) domains, which positions two kinase extension nuclease (KEN) domains for asymmetric RNA recognition. One KEN protomer recognizes an identity nucleotide (U), whereas the other protomer cleaves RNA between nucleotides +1 and +2. The coordinated action of the ANK, KH, and KEN domains thereby provides regulated, sequence-specific cleavage of viral and host RNA targets by RNase L.</p> |
DOI | 10.1126/science.1249845 |
Alternate Journal | Science |
PubMed ID | 24578532 |
PubMed Central ID | PMC4731867 |
Grant List | P41 GM111244 / GM / NIGMS NIH HHS / United States R01 GM110161 / GM / NIGMS NIH HHS / United States T32 GM007388 / GM / NIGMS NIH HHS / United States |