The RNase H-like superfamily: new members, comparative structural analysis and evolutionary classification.
Ribonuclease H-like (RNHL) superfamily, also called the retroviral integrase superfamily, groups together numerous enzymes involved in nucleic acid metabolism and implicated in many biological processes, including replication, homologous recombination, DNA repair, transposition and RNA interference. The RNHL superfamily proteins show extensive divergence of sequences and structures. We conducted database searches to identify members of the RNHL superfamily (including those previously unknown), yielding >60 000 unique domain sequences. Our analysis led to the identification of new RNHL superfamily members, such as RRXRR (PF14239), DUF460 (PF04312, COG2433), DUF3010 (PF11215), DUF429 (PF04250 and COG2410, COG4328, COG4923), DUF1092 (PF06485), COG5558, OrfB_IS605 (PF01385, COG0675) and Peptidase_A17 (PF05380). Based on the clustering analysis we grouped all identified RNHL domain sequences into 152 families. Phylogenetic studies revealed relationships between these families, and suggested a possible history of the evolution of RNHL fold and its active site. Our results revealed clear division of the RNHL superfamily into exonucleases and endonucleases. Structural analyses of features characteristic for particular groups revealed a correlation between the orientation of the C-terminal helix with the exonuclease/endonuclease function and the architecture of the active site. Our analysis provides a comprehensive picture of sequence-structure-function relationships in the RNHL superfamily that may guide functional studies of the previously uncharacterized protein families.
Laboratory of Bioinformatics and Protein Engineering, International Institute of Molecular and Cell Biology, ul. Ks. Trojdena 4, PL-02-109 Warsaw, Poland, Department of Molecular Physiology and Biological Physics, University of Virginia, 1340 Jefferson Park Avenue, Charlottesville, VA USA-22908, USA, Bioinformatics Laboratory, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, Umultowska 89, PL-61-614 Poznan, Poland, Laboratory of Bioinformatics and Systems Biology, Centre of New Technologies, University of Warsaw, Zwirki i Wigury 93, PL-02-089 Warsaw, Poland, Institute of Biochemistry and Biophysics PAS, Pawinskiego 5A, PL-02-106 Warsaw, Poland and Laboratory of Protein Structure, International Institute of Molecular and Cell Biology, ul. Ks. Trojdena 4, PL-02-109 Warsaw, Poland.
Karolina A
KA
Majorek
Stanislaw
S
Dunin-Horkawicz
Kamil
K
Steczkiewicz
Anna
A
Muszewska
Marcin
M
Nowotny
Krzysztof
K
Ginalski
Janusz M
JM
Bujnicki
D016000:Cluster Analysis; D019143:Evolution, Molecular; D005092:Exonucleases / Q000145:classification; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D016914:Ribonuclease H / Q000737:chemistry* / Q000145:classification* / Q000235:genetics; D016415:Sequence Alignment
D005092:Exonucleases; D016914:Ribonuclease H