3PUF

Crystal structure of human RNase H2 complex

Summary for 3PUF

• Entry DOI: 10.2210/pdb3puf/pdb
• Descriptor: Ribonuclease H2 subunit A, Ribonuclease H2 subunit B, Ribonuclease H2 subunit C, ... (4 entities in total)
• Functional Keywords: rnase h fold, triple barrel fold, hydrolase, rnase h
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus (Probable): O75792 Q5TBB1 Q8TDP1
• Total number of polymer chains: 18
• Total formula weight: 465896.12

Authors

Figiel, M.,Chon, H.,Cerritelli, S.M.,Cybulska, M.,Crouch, R.J.,Nowotny, M. (deposition date: 2010-12-04, release date: 2010-12-22, Last modification date: 2023-11-01)

Primary citation

Figiel, M.,Chon, H.,Cerritelli, S.M.,Cybulska, M.,Crouch, R.J.,Nowotny, M.
The structural and biochemical characterization of human RNase H2 complex reveals the molecular basis for substrate recognition and Aicardi-Goutieres syndrome defects.
J.Biol.Chem., 286:10540-10550, 2011

PubMed Abstract: RNase 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-Goutières syndrome, a severe autoimmune disorder. The 3.1 Å crystal structure of human RNase H2 presented here allowed us to map the positions of all 29 mutations found in Aicardi-Goutières 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.

PubMed: 21177858
DOI: 10.1074/jbc.M110.181974

Experimental method

X-RAY DIFFRACTION (3.1 Å)