3puf | pdb_00003puf
Crystal structure of human RNase H2 complex
Structural highlights
DiseaseRNH2A_HUMAN Aicardi-Goutieres syndrome. The disease is caused by mutations affecting the gene represented in this entry. FunctionRNH2A_HUMAN Catalytic subunit of RNase HII, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA replication, possibly by mediating the removal of lagging-strand Okazaki fragment RNA primers during DNA replication. Mediates the excision of single ribonucleotides from DNA:RNA duplexes.[1] [2] Publication Abstract from PubMedRNase H2 cleaves RNA sequences that are part of RNA/DNA hybrids or that are incorporated into DNA, thus, preventing genomic instability and the accumulation of aberrant nucleic acid, which in humans induces Aicardi-Goutieres syndrome, a severe autoimmune disorder. The 3.1 A crystal structure of human RNase H2 presented here allowed us to map the positions of all 29 mutations found in Aicardi-Goutieres syndrome patients, several of which were not visible in the previously reported mouse RNase H2. We propose the possible effects of these mutations on the protein stability and function. Bacterial and eukaryotic RNases H2 differ in composition and substrate specificity. Bacterial RNases H2 are monomeric proteins and homologs of the eukaryotic RNases H2 catalytic subunit, which in addition possesses two accessory proteins. The eukaryotic RNase H2 heterotrimeric complex recognizes RNA/DNA hybrids and (5')RNA-DNA(3')/DNA junction hybrids as substrates with similar efficiency, whereas bacterial RNases H2 are highly specialized in the recognition of the (5')RNA-DNA(3') junction and very poorly cleave RNA/DNA hybrids in the presence of Mg(2+) ions. Using the crystal structure of the Thermotoga maritima RNase H2-substrate complex, we modeled the human RNase H2-substrate complex and verified the model by mutational analysis. Our model indicates that the difference in substrate preference stems from the different position of the crucial tyrosine residue involved in substrate binding and recognition. The structural and biochemical characterization of human RNase H2 complex reveals the molecular basis for substrate recognition and Aicardi-Goutieres syndrome defects.,Figiel M, Chon H, Cerritelli SM, Cybulska M, Crouch RJ, Nowotny M J Biol Chem. 2011 Mar 25;286(12):10540-50. Epub 2010 Dec 22. PMID:21177858[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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